DGIdb - GABRA1 Gene Record

GABRA1 2554 Druggable Genome

Alternate Names:

2554
GAMMA-AMINOBUTYRIC ACID TYPE A RECEPTOR ALPHA1 SUBUNIT
GABRA1
ECA4
EIEE19
EJM
EJM5
137160
4075
ENSG00000022355
OTTHUMG00000163586
GABA(A) receptor subunit alpha-1
Gamma-aminobutyric acid receptor subunit alpha-1
P14867
GBRA1_HUMAN
BE0008668
BE0000795
404
NP_000797
NM_000806
BE0004797
GAMMA-AMINOBUTYRIC-ACID RECEPTOR ALPHA-1 SUBUNIT PRECURSOR (GABA(A) RECEPTOR). [SOURCE:UNIPROT/SWISSPROT;ACC:P14867]
GABA<sub>A</sub> receptor α1 subunit
GABRD
PA28489
GABA(A) receptor alpha-1
T51487
gamma-aminobutyric acid type A receptor subunit alpha1

Gene Info:

GuideToPharmacology Gene Category Name	GABA<sub>A</sub> receptors
GuideToPharmacology Gene Category ID	72
Human Readable Name	ION CHANNEL
Interpro Short Name	Neur_chan_lig-bd
Human Readable Name	DRUGGABLE GENOME
Interpro Name	Neurotransmitter-gated ion-channel
Interpro Acc	IPR006202
Interpro Name	Neurotransmitter-gated ion-channel ligand-binding
Interpro Type	Domain
Interpro Acc	IPR006201
Interpro Short Name	Neur_channel
Uniprot Evidence	1: Evidence at protein level
Uniprot Status	Swiss-Prot
Interpro Type	Family
Target Subclass	Channels
Target Subclass	Ligand_gated_ion_channels
Target Subclass	cys-loop
Target Main Class	Receptors
Transmembrane Helix Count	4
Target Class	Receptors
Target Subclass	TC:1.A.9
Gene Biotype	PROTEIN_CODING

(11 More Sources)

Gene Categories: Category Details

TRANSPORTER
ION CHANNEL
DRUGGABLE GENOME

Publications:

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.
Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.
Zhu S et al., 2018, Structure of a human synaptic GABA<sub>A</sub> receptor., Nature
Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem
Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.
Feigenspan et al., 2004, Electrophysiological properties of mouse horizontal cell GABAA receptors., J. Neurophysiol.
Davies et al., 2001, Pressure-sensitive and -insensitive coupling in gamma-aminobutyric acid(A) receptors., Psychopharmacology (Berl.)
Whiting, 2003, The GABAA receptor gene family: new opportunities for drug development., Curr Opin Drug Discov Devel
Mehta et al., 1999, An update on GABAA receptors., Brain Res. Brain Res. Rev.
Rahman et al., 2006, GABA-site antagonism and pentobarbital actions do not depend on the alpha-subunit type in the recombinant rat GABA receptor., Acta Physiol (Oxf)
Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.
Krasowski et al., 1999, General anaesthetic actions on ligand-gated ion channels., Cell. Mol. Life Sci.
Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov
Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov
Steinbach et al., 2001, Modulation of GABA(A) receptor channel gating by pentobarbital., J. Physiol. (Lond.)
Koltchine et al., 1996, Chimeric GABAA/glycine receptors: expression and barbiturate pharmacology., Neuropharmacology
Verster et al., 2004, Clinical pharmacology, clinical efficacy, and behavioral toxicity of alprazolam: a review of the literature., CNS Drug Rev
McCracken et al., 2010, A transmembrane amino acid in the GABAA receptor β2 subunit critical for the actions of alcohols and anesthetics., J. Pharmacol. Exp. Ther.
Seo et al., 2010, Genetic reduction of GABA(A) receptor gamma2 subunit expression potentiates the immobilizing action of isoflurane., Neurosci. Lett.
Braga et al., 2009, Topiramate reduces excitability in the basolateral amygdala by selectively inhibiting GluK1 (GluR5) kainate receptors on interneurons and positively modulating GABAA receptors on principal neurons., J. Pharmacol. Exp. Ther.
Nowakowska et al., 2009, Memory improving and antidepressant effects of topiramate in rats., Arzneimittelforschung
Garnett WR, 2000, Clinical pharmacology of topiramate: a review., Epilepsia
Chung JY et al., 2014, Efficacy of zonisamide in migraineurs with nonresponse to topiramate., Biomed Res Int
Buckley et al., 1998, Can the fatal toxicity of antidepressant drugs be predicted with pharmacological and toxicological data?, Drug Saf
Wei et al., 1990, [Comparison of the affinities of amoxapine and loxapine for various receptors in rat brain and the receptor down-regulation after chronic administration]., Yao Xue Xue Bao
de Fiebre et al., 1992, Classical genetic analyses of responses to sedative-hypnotic drugs in crosses derived from long-sleep and short-sleep mice., Alcohol. Clin. Exp. Res.
Lahti et al., 1983, Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine., Neuropharmacology
Sethy et al., 1984, Determination of biological activity of adinazolam and its metabolites., J. Pharm. Pharmacol.
Amin et al., 1997, Two tyrosine residues on the alpha subunit are crucial for benzodiazepine binding and allosteric modulation of gamma-aminobutyric acidA receptors., Mol. Pharmacol.
Wingrove et al., 2002, Mechanism of alpha-subunit selectivity of benzodiazepine pharmacology at gamma-aminobutyric acid type A receptors., Eur. J. Pharmacol.
Whitwam et al., 1995, Pharmacology of flumazenil., Acta Anaesthesiol Scand Suppl
Iorio et al., 1984, Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites., Life Sci.
Wamsley et al., 1985, Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain., Pharmacol. Biochem. Behav.
Rho et al., 1997, Barbiturate-like actions of the propanediol dicarbamates felbamate and meprobamate., J. Pharmacol. Exp. Ther.
Gonzalez et al., 2009, Carisoprodol-mediated modulation of GABAA receptors: in vitro and in vivo studies., J. Pharmacol. Exp. Ther.
Greenblatt et al., 2001, Divergence of volatile anesthetic effects in inhibitory neurotransmitter receptors., Anesthesiology
Franks, 2006, Molecular targets underlying general anaesthesia., Br. J. Pharmacol.
Grasshoff et al., 2006, Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats., Br J Anaesth
Olsen et al., 2011, GABA(A) receptors as molecular targets of general anesthetics: identification of binding sites provides clues to allosteric modulation., Can J Anaesth
Roden et al., 2010, Altered GABA(A) receptor subunit expression and pharmacology in human Angelman syndrome cortex., Neurosci. Lett.
Nutt et al., 2010, Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics., J. Psychopharmacol. (Oxford)
Hanson et al., 2008, Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different., J. Med. Chem.
Wadworth AN et al., 1993, Zopiclone. A review of its pharmacological properties and therapeutic efficacy as an hypnotic., Drugs Aging
Dixon CL et al., 2015, Zolpidem and eszopiclone prime α1β2γ2 GABAA receptors for longer duration of activity., Br J Pharmacol
Döble A et al., 1995, The mechanism of action of zopiclone., Eur Psychiatry
Husain SS et al., 2006, Synthesis of trifluoromethylaryl diazirine and benzophenone derivatives of etomidate that are potent general anesthetics and effective photolabels for probing sites on ligand-gated ion channels., J Med Chem
Husain SS et al., 2010, p-Trifluoromethyldiazirinyl-etomidate: a potent photoreactive general anesthetic derivative of etomidate that is selective for ligand-gated cationic ion channels., J Med Chem
Martin et al., 2009, Etomidate targets alpha5 gamma-aminobutyric acid subtype A receptors to regulate synaptic plasticity and memory blockade., Anesthesiology
Desai et al., 2009, Gamma-amino butyric acid type A receptor mutations at beta2N265 alter etomidate efficacy while preserving basal and agonist-dependent activity., Anesthesiology
Pritchett et al., 1990, Gamma-aminobutyric acidA receptor alpha 5-subunit creates novel type II benzodiazepine receptor pharmacology., J. Neurochem.
Smith et al., 2001, Effect of alpha subunit on allosteric modulation of ion channel function in stably expressed human recombinant gamma-aminobutyric acid(A) receptors determined using (36)Cl ion flux., Mol. Pharmacol.
Vlainić et al., 2009, Effects of acute and repeated zolpidem treatment on pentylenetetrazole-induced seizure threshold and on locomotor activity: comparison with diazepam., Neuropharmacology
Tan KR et al., 2011, Hooked on benzodiazepines: GABAA receptor subtypes and addiction., Trends Neurosci
Sramka M et al., 1975, Surgical complication of posterior hypothalamotomy., Confin Neurol
Billard et al., 1988, Selective affinity of the benzodiazepines quazepam and 2-oxo-quazepam for BZ1 binding site and demonstration of 3H-2-oxo-quazepam as a BZ1 selective radioligand., Life Sci.
Meldrum et al., 1986, Benzodiazepine receptors and their relationship to the treatment of epilepsy., Epilepsia
Nakatsuka et al., 1985, Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity., Life Sci.
Franks NP et al., 1994, Molecular and cellular mechanisms of general anaesthesia., Nature
Qi ZH et al., 2007, Protein kinase C epsilon regulates gamma-aminobutyrate type A receptor sensitivity to ethanol and benzodiazepines through phosphorylation of gamma2 subunits., J Biol Chem
Baburin et al., 2008, Estimating the efficiency of benzodiazepines on GABA(A) receptors comprising gamma1 or gamma2 subunits., Br. J. Pharmacol.
Mandrioli et al., 2008, Benzodiazepine metabolism: an analytical perspective., Curr. Drug Metab.
Derry et al., 2004, Identification of a residue in the gamma-aminobutyric acid type A receptor alpha subunit that differentially affects diazepam-sensitive and -insensitive benzodiazepine site binding., J. Neurochem.
Terzano et al., 2003, New drugs for insomnia: comparative tolerability of zopiclone, zolpidem and zaleplon., Drug Saf
Sanger et al., 1999, Discriminative stimulus effects of drugs acting at GABA(A) receptors: differential profiles and receptor selectivity., Pharmacol. Biochem. Behav.
Patat et al., 2001, Pharmacodynamic profile of Zaleplon, a new non-benzodiazepine hypnotic agent., Hum Psychopharmacol
Barbera et al., 2005, Benefit-risk assessment of zaleplon in the treatment of insomnia., Drug Saf
Agmo et al., 1998, Interactions between dopamine and GABA in the control of ambulatory activity and neophobia in the mouse., Pharmacol. Biochem. Behav.
Grech et al., 1993, Pentobarbital-like discriminative stimulus effects of direct GABA agonists in rats., Psychopharmacology (Berl.)
Fadda et al., 1985, Suppression by progabide of ethanol withdrawal syndrome in rats., Eur. J. Pharmacol.
Ramerstorfer et al., 2010, The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes., Eur. J. Pharmacol.
Sanger, 2004, The pharmacology and mechanisms of action of new generation, non-benzodiazepine hypnotic agents., CNS Drugs
Skerritt et al., 1983, Enhancement of GABA binding by benzodiazepines and related anxiolytics., Eur. J. Pharmacol.
Zhou BT et al., 2012, Effects of SCN1A and GABA receptor genetic polymorphisms on carbamazepine tolerability and efficacy in Chinese patients with partial seizures: 2-year longitudinal clinical follow-up., CNS Neurosci Ther
Grasshoff et al., 2008, Depression of spinal network activity by thiopental: shift from phasic to tonic GABA(A) receptor-mediated inhibition., Neuropharmacology
Sugimura et al., 2002, Effects of GABAergic agents on anesthesia induced by halothane, isoflurane, and thiamylal in mice., Pharmacol. Biochem. Behav.
Moody et al., 1988, The imidazobenzodiazepine Ro 15-4513 antagonizes methoxyflurane anesthesia., Life Sci.
Moody et al., 1988, Modulation of the benzodiazepine/gamma-aminobutyric acid receptor chloride channel complex by inhalation anesthetics., J. Neurochem.
Krasowski et al., 2000, The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations., Br. J. Pharmacol.
Stewart DS et al., 2011, p-(4-Azipentyl)propofol: a potent photoreactive general anesthetic derivative of propofol., J Med Chem
Braestrup et al., 1978, Pharmacological characterization of benzodiazepine receptors in the brain., Eur. J. Pharmacol.
Miller et al., 1987, Benzodiazepine receptor binding of triazolobenzodiazepines in vivo: increased receptor number with low-dose alprazolam., J. Neurochem.
Giersch et al., 2010, Atypical behavioural effects of lorazepam: clues to the design of novel therapies?, Pharmacol. Ther.
Hedera P et al., 2013, Pharmacotherapy of essential tremor., J Cent Nerv Syst Dis
Cutrer et al., Attenuation by butalbital of capsaicin-induced c-fos-like immunoreactivity in trigeminal nucleus caudalis., Headache
Bymaster et al., 1996, Radioreceptor binding profile of the atypical antipsychotic olanzapine., Neuropsychopharmacology
Brafford MV et al., 2014, Olanzapine: an antiemetic option for chemotherapy-induced nausea and vomiting., J Adv Pract Oncol
Blaschke et al., 1986, [Racemation of the benzodiazepines camazepam and ketazolam and receptor binding of enantiomers]., Arzneimittelforschung
Nishikawa K et al., 2002, Volatile anesthetic actions on the GABAA receptors: contrasting effects of alpha 1(S270) and beta 2(N265) point mutations., Neuropharmacology
Nishikawa K et al., 2003, The actions of sevoflurane and desflurane on the gamma-aminobutyric acid receptor type A: effects of TM2 mutations in the alpha and beta subunits., Anesthesiology
Richter et al., 2010, Intrinsic activation of GABA(A) receptors suppresses epileptiform activity in the cerebral cortex of immature mice., Epilepsia
Law et al., 2008, Gaba receptor insecticide non-competitive antagonists may bind at allosteric modulator sites., Int. J. Neurosci.
Macdonald et al., 1986, Anticonvulsant drugs: mechanisms of action., Adv Neurol
Peters et al., 1988, Modulation of the GABAA receptor by depressant barbiturates and pregnane steroids., Br. J. Pharmacol.
Miller et al., 1988, Acute barbiturate administration increases benzodiazepine receptor binding in vivo., Psychopharmacology (Berl.)
Kirkness et al., 1986, The gamma-aminobutyrate/benzodiazepine receptor from pig brain. Purification and characterization of the receptor complex from cerebral cortex and cerebellum., Biochem. J.
Zaugg J et al., 2011, Identification and characterization of GABA(A) receptor modulatory diterpenes from Biota orientalis that decrease locomotor activity in mice., J Nat Prod
Podhorna et al., 2000, Behavioural effects of a benzodiazepine receptor partial agonist, Ro 19-8022, in the social conflict test in mice., Behav Pharmacol
Tanaka et al., 2008, Comparison of short- and long-acting benzodiazepine-receptor agonists with different receptor selectivity on motor coordination and muscle relaxation following thiopental-induced anesthesia in mice., J. Pharmacol. Sci.
Smeyatsky et al., 1992, The treatment of sleep disorders., S. Afr. Med. J.
Skerritt et al., 1983, Interactions of some anaesthetic, convulsant, and anticonvulsant drugs at GABA-benzodiazepine receptor-ionophore complexes in rat brain synaptosomal membranes., Neurochem. Res.
Williams, 2005, Medications for treating alcohol dependence., Am Fam Physician
Tomlin et al., 1999, Preparation of barbiturate optical isomers and their effects on GABA(A) receptors., Anesthesiology
Earl et al., 2011, Inhibition of recombinant L-type voltage-gated calcium channels by positive allosteric modulators of GABAA receptors., J. Pharmacol. Exp. Ther.
Davies, 2003, The role of GABAA receptors in mediating the effects of alcohol in the central nervous system., J Psychiatry Neurosci
Santhakumar et al., 2007, Ethanol acts directly on extrasynaptic subtypes of GABAA receptors to increase tonic inhibition., Alcohol
Petersen JG et al., 2014, Synthesis and pharmacological evaluation of 6-aminonicotinic acid analogues as novel GABA(A) receptor agonists., Eur J Med Chem
Carta et al., 2006, The muscle relaxant thiocolchicoside is an antagonist of GABAA receptor function in the central nervous system., Neuropharmacology
Mascia et al., 2007, Thiocolchicoside inhibits the activity of various subtypes of recombinant GABA(A) receptors expressed in Xenopus laevis oocytes., Eur. J. Pharmacol.
Keppel Hesselink JM, 2017, Phenytoin: a step by step insight into its multiple mechanisms of action-80 years of mechanistic studies in neuropharmacology., J Neurol
Sousa et al., 1997, Interactions of the neurosteroid dehydroepiandrosterone sulfate with the GABA(A) receptor complex reveals that it may act via the picrotoxin site., J. Pharmacol. Exp. Ther.
Anzini M et al., 2011, New insight into the central benzodiazepine receptor-ligand interactions: design, synthesis, biological evaluation, and molecular modeling of 3-substituted 6-phenyl-4H-imidazo[1,5-a][1,4]benzodiazepines and related compounds., J Med Chem
Braga MF et al., 2002, Lamotrigine reduces spontaneous and evoked GABAA receptor-mediated synaptic transmission in the basolateral amygdala: implications for its effects in seizure and affective disorders., Neuropharmacology
Wang JF et al., 2002, Lamotrigine increases gene expression of GABA-A receptor beta3 subunit in primary cultured rat hippocampus cells., Neuropsychopharmacology
Abelaira HM et al., 2012, Lamotrigine treatment reverses depressive-like behavior and alters BDNF levels in the brains of maternally deprived adult rats., Pharmacol Biochem Behav
Meldrum BS, 1996, Update on the mechanism of action of antiepileptic drugs., Epilepsia
Molinaro G et al., 2009, Memantine treatment reduces the expression of the K(+)/Cl(-) cotransporter KCC2 in the hippocampus and cerebral cortex, and attenuates behavioural responses mediated by GABA(A) receptor activation in mice., Brain Res
Fernandes H et al., 2014, Mexazolam: clinical efficacy and tolerability in the treatment of anxiety., Neurol Ther
Kilb W et al., 2017, Taurine as an Essential Neuromodulator during Perinatal Cortical Development., Front Cell Neurosci
Clegg NJ et al., 2012, ARN-509: a novel antiandrogen for prostate cancer treatment., Cancer Res
Gonzalez LA et al., 2009, Abuse Potential of Soma: the GABA(A) Receptor as a Target., Mol Cell Pharmacol
Kumar M et al., 2016, Assessment of direct gating and allosteric modulatory effects of meprobamate in recombinant GABA(A) receptors., Eur J Pharmacol
Fisher JL, 2009, The anti-convulsant stiripentol acts directly on the GABA(A) receptor as a positive allosteric modulator., Neuropharmacology
Huen MS et al., 2003, Naturally occurring 2'-hydroxyl-substituted flavonoids as high-affinity benzodiazepine site ligands., Biochem Pharmacol

CLONAZEPAM GABRA1

Interaction Types & Directionality:

allosteric modulator

positive modulator (activating)

ligand

Interaction Info:

Trial Name JZP-8

Novel drug target Established target

Details of the Assay for Interaction Assay using recombinant GABAA channels with subunit composition; α1β1γ2.

Publications:

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

ALPRAZOLAM GABRA1

Interaction Types & Directionality:

positive modulator (activating)

allosteric modulator

ligand

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Specific Binding Site for Interaction benzodiazepine site

Publications:

Verster et al., 2004, Clinical pharmacology, clinical efficacy, and behavioral toxicity of alprazolam: a review of the literature., CNS Drug Rev

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

TRIAZOLAM GABRA1

Interaction Types & Directionality:

potentiator

positive modulator (activating)

allosteric modulator

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Trial Name ARX-03, sufentanil + triazolam NanoTab

Publications:

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

DESFLURANE GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Trial Name -

Novel drug target Established target

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Publications:

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

FLUMAZENIL GABRA1

Interaction Types & Directionality:

antagonist (inhibitory)

allosteric modulator

positive modulator (activating)

Interaction Info:

Specific Binding Site for Interaction benzodiazepine site

Details of the Assay for Interaction Affinity measured using α1β3γ2 receptors.

Specific Action of the Ligand Antagonist

Publications:

Wingrove et al., 2002, Mechanism of alpha-subunit selectivity of benzodiazepine pharmacology at gamma-aminobutyric acid type A receptors., Eur. J. Pharmacol.

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Whitwam et al., 1995, Pharmacology of flumazenil., Acta Anaesthesiol Scand Suppl

BICUCULLINE GABRA1

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Binding Site for Interaction GABA site

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Publications:

Qi ZH et al., 2007, Protein kinase C epsilon regulates gamma-aminobutyrate type A receptor sensitivity to ethanol and benzodiazepines through phosphorylation of gamma2 subunits., J Biol Chem

DIAZEPAM GABRA1

Interaction Types & Directionality:

allosteric modulator

potentiator

positive modulator (activating)

Interaction Info:

Direct Interaction? True

Endogenous Drug? False

Specific Action of the Ligand Positive

Publications:

Derry et al., 2004, Identification of a residue in the gamma-aminobutyric acid type A receptor alpha subunit that differentially affects diazepam-sensitive and -insensitive benzodiazepine site binding., J. Neurochem.

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

MUSCIMOL GABRA1

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Full agonist

Publications:

Stewart DS et al., 2011, p-(4-Azipentyl)propofol: a potent photoreactive general anesthetic derivative of propofol., J Med Chem
THIAMYLAL SODIUM GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Publications:
ISOGUVACINE GABRA1

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Specific Binding Site for Interaction GABA site

Specific Action of the Ligand Full agonist

Endogenous Drug? False

Publications:
ADIPIPLON GABRA1

Interaction Types & Directionality:

partial agonist (activating)

Interaction Info:

Trial Name NG2-73

Novel drug target Established target

Direct Interaction yes

Publications:
MIDAZOLAM HYDROCHLORIDE GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Publications:
INDIPLON GABRA1

Interaction Types & Directionality:

positive modulator (activating)

allosteric modulator

Interaction Info:

Mechanism of Interaction GABA receptor alpha-1 subunit positive allosteric modulator

Direct Interaction yes

Trial Name Indiplon

Publications:
BRETAZENIL GABRA1

Interaction Types & Directionality:

allosteric modulator

Interaction Info:

Specific Binding Site for Interaction benzodiazepine site

Specific Action of the Ligand Full agonist

Endogenous Drug? False

Publications:
GABAZINE GABRA1

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Binding Site for Interaction GABA site

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Publications:
LOREDIPLON GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; benzodiazepine site positive allosteric modulator

Publications:
ZOLPIDEM TARTRATE GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA A receptor alpha-1/beta-1/gamma-2 positive allosteric modulator

Direct Interaction yes

Publications:
CHLORDIAZEPOXIDE HYDROCHLORIDE GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Publications:
PF-06372865 GABRA1

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel agonist

Direct Interaction yes

Publications:
GABOXADOL GABRA1

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; agonist GABA site agonist

Direct Interaction yes

Specific Binding Site for Interaction GABA site

Publications:
SECOBARBITAL SODIUM GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Publications:
OCINAPLON GABRA1

Interaction Types & Directionality:

allosteric modulator

Interaction Info:

Trial Name ocinaplon

Novel drug target Established target

Specific Binding Site for Interaction benzodiazepine site

Publications:
BUTABARBITAL SODIUM GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Publications:
PENTOBARBITAL SODIUM GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Publications:
RESEQUINIL GABRA1

Interaction Types & Directionality:

inverse agonist (inhibitory)

Interaction Info:

Mechanism of Interaction GABA-A receptor; benzodiazepine site inverse agonist

Direct Interaction yes

Publications:
METHOHEXITAL SODIUM GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Publications:
CLORAZEPATE DIPOTASSIUM GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Publications:
MK-0777 GABRA1

Interaction Types & Directionality:

allosteric modulator

Interaction Info:

Specific Binding Site for Interaction benzodiazepine site

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Publications:
PROPOFOL GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Publications:
THIOPENTAL SODIUM GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Publications:

PENTOBARBITAL GABRA1

Interaction Types & Directionality:

positive modulator (activating)

potentiator

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Trial Name -

Publications:

Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.

Feigenspan et al., 2004, Electrophysiological properties of mouse horizontal cell GABAA receptors., J. Neurophysiol.

Davies et al., 2001, Pressure-sensitive and -insensitive coupling in gamma-aminobutyric acid(A) receptors., Psychopharmacology (Berl.)

METHOHEXITAL GABRA1

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

Publications:

Koltchine et al., 1996, Chimeric GABAA/glycine receptors: expression and barbiturate pharmacology., Neuropharmacology

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

CLORAZEPIC ACID GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Trial Name -

Novel drug target Established target

Publications:

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

ISOFLURANE GABRA1

Interaction Types & Directionality:

agonist (activating)

positive modulator (activating)

Interaction Info:

Trial Name -

Novel drug target Established target

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Publications:

McCracken et al., 2010, A transmembrane amino acid in the GABAA receptor β2 subunit critical for the actions of alcohols and anesthetics., J. Pharmacol. Exp. Ther.

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

TOPIRAMATE GABRA1

Interaction Types & Directionality:

agonist (activating)

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive modulator

Direct Interaction yes

Trial Name topiramate controlled release,Trokesa

Publications:

Braga et al., 2009, Topiramate reduces excitability in the basolateral amygdala by selectively inhibiting GluK1 (GluR5) kainate receptors on interneurons and positively modulating GABAA receptors on principal neurons., J. Pharmacol. Exp. Ther.

Nowakowska et al., 2009, Memory improving and antidepressant effects of topiramate in rats., Arzneimittelforschung

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

AMOXAPINE GABRA1

Interaction Types & Directionality:

antagonist (inhibitory)

binder

Interaction Info:

Publications:

Buckley et al., 1998, Can the fatal toxicity of antidepressant drugs be predicted with pharmacological and toxicological data?, Drug Saf

Wei et al., 1990, [Comparison of the affinities of amoxapine and loxapine for various receptors in rat brain and the receptor down-regulation after chronic administration]., Yao Xue Xue Bao

METHYPRYLON GABRA1

Interaction Types & Directionality:

agonist (activating)

positive modulator (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Trial Name -

Publications:

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

ADINAZOLAM GABRA1

Interaction Types & Directionality:

potentiator

ligand

positive modulator (activating)

Interaction Info:

Novel drug target Established target

Trial Name -

Publications:

Lahti et al., 1983, Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine., Neuropharmacology

Sethy et al., 1984, Determination of biological activity of adinazolam and its metabolites., J. Pharm. Pharmacol.

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

CINOLAZEPAM GABRA1

Interaction Types & Directionality:

potentiator

ligand

positive modulator (activating)

Interaction Info:

Trial Name -

Novel drug target Established target

Publications:

Amin et al., 1997, Two tyrosine residues on the alpha subunit are crucial for benzodiazepine binding and allosteric modulation of gamma-aminobutyric acidA receptors., Mol. Pharmacol.

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem

CLOBAZAM GABRA1

Interaction Types & Directionality:

positive modulator (activating)

ligand

Interaction Info:

Novel drug target Established target

Trial Name Clobazam

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Publications:

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

MIDAZOLAM GABRA1

Interaction Types & Directionality:

potentiator

ligand

positive modulator (activating)

Interaction Info:

Trial Name -

Novel drug target Established target

Publications:

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

HALAZEPAM GABRA1

Interaction Types & Directionality:

positive modulator (activating)

potentiator

ligand

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Trial Name -

Publications:

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

MEPROBAMATE GABRA1

Interaction Types & Directionality:

agonist (activating)

positive modulator (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; anion channel agonist

Trial Name -

Publications:

Rho et al., 1997, Barbiturate-like actions of the propanediol dicarbamates felbamate and meprobamate., J. Pharmacol. Exp. Ther.

Gonzalez et al., 2009, Carisoprodol-mediated modulation of GABAA receptors: in vitro and in vivo studies., J. Pharmacol. Exp. Ther.

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

ENFLURANE GABRA1

Interaction Types & Directionality:

positive modulator (activating)

potentiator

Interaction Info:

Trial Name -

Novel drug target Established target

Mechanism of Interaction GABA-A receptor; anion channel positive modulator

Publications:

Greenblatt et al., 2001, Divergence of volatile anesthetic effects in inhibitory neurotransmitter receptors., Anesthesiology

Franks, 2006, Molecular targets underlying general anaesthesia., Br. J. Pharmacol.

Grasshoff et al., 2006, Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats., Br J Anaesth

MEPHOBARBITAL GABRA1

Interaction Types & Directionality:

potentiator

Interaction Info:

Novel drug target Established target

Trial Name -

Publications:

Whiting, 2003, The GABAA receptor gene family: new opportunities for drug development., Curr Opin Drug Discov Devel

Mehta et al., 1999, An update on GABAA receptors., Brain Res. Brain Res. Rev.

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

ESZOPICLONE GABRA1

Interaction Types & Directionality:

potentiator

positive modulator (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Trial Name Lunesta

Publications:

Nutt et al., 2010, Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics., J. Psychopharmacol. (Oxford)

Hanson et al., 2008, Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different., J. Med. Chem.

Wadworth AN et al., 1993, Zopiclone. A review of its pharmacological properties and therapeutic efficacy as an hypnotic., Drugs Aging

ETOMIDATE GABRA1

Interaction Types & Directionality:

agonist (activating)

positive modulator (activating)

Interaction Info:

Novel drug target Established target

Trial Name -

Mechanism of Interaction GABA-A receptor; anion channel positive modulator

Publications:

Husain SS et al., 2006, Synthesis of trifluoromethylaryl diazirine and benzophenone derivatives of etomidate that are potent general anesthetics and effective photolabels for probing sites on ligand-gated ion channels., J Med Chem

Husain SS et al., 2010, p-Trifluoromethyldiazirinyl-etomidate: a potent photoreactive general anesthetic derivative of etomidate that is selective for ligand-gated cationic ion channels., J Med Chem

Martin et al., 2009, Etomidate targets alpha5 gamma-aminobutyric acid subtype A receptors to regulate synaptic plasticity and memory blockade., Anesthesiology

PRAZEPAM GABRA1

Interaction Types & Directionality:

potentiator

positive modulator (activating)

ligand

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Trial Name -

Publications:

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

ZOLPIDEM GABRA1

Interaction Types & Directionality:

allosteric modulator

potentiator

agonist (activating)

Interaction Info:

Details of the Assay for Interaction Assay using recombinant GABAA channels with subunit composition; α1β3γ2.

Specific Action of the Ligand Positive

Endogenous Drug? False

Publications:

Pritchett et al., 1990, Gamma-aminobutyric acidA receptor alpha 5-subunit creates novel type II benzodiazepine receptor pharmacology., J. Neurochem.

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

TALBUTAL GABRA1

Interaction Types & Directionality:

positive modulator (activating)

potentiator

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Trial Name -

Publications:

Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.

Whiting, 2003, The GABAA receptor gene family: new opportunities for drug development., Curr Opin Drug Discov Devel

Mehta et al., 1999, An update on GABAA receptors., Brain Res. Brain Res. Rev.

QUAZEPAM GABRA1

Interaction Types & Directionality:

positive modulator (activating)

potentiator

ligand

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Trial Name -

Publications:

Billard et al., 1988, Selective affinity of the benzodiazepines quazepam and 2-oxo-quazepam for BZ1 binding site and demonstration of 3H-2-oxo-quazepam as a BZ1 selective radioligand., Life Sci.

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

FLUDIAZEPAM GABRA1

Interaction Types & Directionality:

potentiator

Interaction Info:

Trial Name -

Novel drug target Established target

Publications:

Nakatsuka et al., 1985, Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity., Life Sci.

SEVOFLURANE GABRA1

Interaction Types & Directionality:

positive modulator (activating)

agonist (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Trial Name -

Publications:

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

Franks NP et al., 1994, Molecular and cellular mechanisms of general anaesthesia., Nature

CLOTIAZEPAM GABRA1

Interaction Types & Directionality:

potentiator

ligand

positive modulator (activating)

Interaction Info:

Trial Name -

Novel drug target Established target

Publications:

Baburin et al., 2008, Estimating the efficiency of benzodiazepines on GABA(A) receptors comprising gamma1 or gamma2 subunits., Br. J. Pharmacol.

Mandrioli et al., 2008, Benzodiazepine metabolism: an analytical perspective., Curr. Drug Metab.

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

ZALEPLON GABRA1

Interaction Types & Directionality:

positive modulator (activating)

potentiator

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA A receptor alpha-1/beta-1/gamma-2 positive allosteric modulator

Trial Name AZ-007, Staccato zaleplon

Publications:

Terzano et al., 2003, New drugs for insomnia: comparative tolerability of zopiclone, zolpidem and zaleplon., Drug Saf

Sanger et al., 1999, Discriminative stimulus effects of drugs acting at GABA(A) receptors: differential profiles and receptor selectivity., Pharmacol. Biochem. Behav.

Patat et al., 2001, Pharmacodynamic profile of Zaleplon, a new non-benzodiazepine hypnotic agent., Hum Psychopharmacol

BUTABARBITAL GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Novel drug target Established target

Trial Name -

Publications:

Mehta et al., 1999, An update on GABAA receptors., Brain Res. Brain Res. Rev.

Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.

PROGABIDE GABRA1

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Novel drug target Established target

Trial Name -

Publications:

Agmo et al., 1998, Interactions between dopamine and GABA in the control of ambulatory activity and neophobia in the mouse., Pharmacol. Biochem. Behav.

Grech et al., 1993, Pentobarbital-like discriminative stimulus effects of direct GABA agonists in rats., Psychopharmacology (Berl.)

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

ZOPICLONE GABRA1

Interaction Types & Directionality:

potentiator

Interaction Info:

Trial Name -

Novel drug target Established target

Publications:

Ramerstorfer et al., 2010, The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes., Eur. J. Pharmacol.

Sanger, 2004, The pharmacology and mechanisms of action of new generation, non-benzodiazepine hypnotic agents., CNS Drugs

Nutt et al., 2010, Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics., J. Psychopharmacol. (Oxford)

METHARBITAL GABRA1

Interaction Types & Directionality:

potentiator

positive modulator (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Trial Name -

Publications:

Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.

Whiting, 2003, The GABAA receptor gene family: new opportunities for drug development., Curr Opin Drug Discov Devel

Mehta et al., 1999, An update on GABAA receptors., Brain Res. Brain Res. Rev.

THIAMYLAL GABRA1

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Novel drug target Established target

Trial Name -

Publications:

Grasshoff et al., 2008, Depression of spinal network activity by thiopental: shift from phasic to tonic GABA(A) receptor-mediated inhibition., Neuropharmacology

Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.

Whiting, 2003, The GABAA receptor gene family: new opportunities for drug development., Curr Opin Drug Discov Devel

THIOPENTAL GABRA1

Interaction Types & Directionality:

potentiator

Interaction Info:

Novel drug target Established target

Trial Name -

Publications:

Whiting, 2003, The GABAA receptor gene family: new opportunities for drug development., Curr Opin Drug Discov Devel

Mehta et al., 1999, An update on GABAA receptors., Brain Res. Brain Res. Rev.

Grasshoff et al., 2008, Depression of spinal network activity by thiopental: shift from phasic to tonic GABA(A) receptor-mediated inhibition., Neuropharmacology

METHOXYFLURANE GABRA1

Interaction Types & Directionality:

agonist (activating)

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive modulator

Direct Interaction yes

Publications:

Moody et al., 1988, The imidazobenzodiazepine Ro 15-4513 antagonizes methoxyflurane anesthesia., Life Sci.

Moody et al., 1988, Modulation of the benzodiazepine/gamma-aminobutyric acid receptor chloride channel complex by inhalation anesthetics., J. Neurochem.

Krasowski et al., 2000, The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations., Br. J. Pharmacol.

ESTAZOLAM GABRA1

Interaction Types & Directionality:

positive modulator (activating)

potentiator

ligand

Interaction Info:

Trial Name -

Novel drug target Established target

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Publications:

Braestrup et al., 1978, Pharmacological characterization of benzodiazepine receptors in the brain., Eur. J. Pharmacol.

Miller et al., 1987, Benzodiazepine receptor binding of triazolobenzodiazepines in vivo: increased receptor number with low-dose alprazolam., J. Neurochem.

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

CHLORDIAZEPOXIDE GABRA1

Interaction Types & Directionality:

positive modulator (activating)

ligand

Interaction Info:

Trial Name -

Novel drug target Established target

Direct Interaction yes

Publications:

Skerritt et al., 1983, Enhancement of GABA binding by benzodiazepines and related anxiolytics., Eur. J. Pharmacol.

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem

TEMAZEPAM GABRA1

Interaction Types & Directionality:

potentiator

positive modulator (activating)

ligand

Interaction Info:

Novel drug target Established target

Trial Name -

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Publications:

Giersch et al., 2010, Atypical behavioural effects of lorazepam: clues to the design of novel therapies?, Pharmacol. Ther.

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

PRIMIDONE GABRA1

Interaction Types & Directionality:

positive modulator (activating)

potentiator

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Trial Name -

Publications:

Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.

Whiting, 2003, The GABAA receptor gene family: new opportunities for drug development., Curr Opin Drug Discov Devel

Mehta et al., 1999, An update on GABAA receptors., Brain Res. Brain Res. Rev.

OXAZEPAM GABRA1

Interaction Types & Directionality:

positive modulator (activating)

potentiator

ligand

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Trial Name -

Publications:

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

HEPTABARBITAL GABRA1

Interaction Types & Directionality:

potentiator

Interaction Info:

Publications:

Whiting, 2003, The GABAA receptor gene family: new opportunities for drug development., Curr Opin Drug Discov Devel

Mehta et al., 1999, An update on GABAA receptors., Brain Res. Brain Res. Rev.

Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.

BUTALBITAL GABRA1

Interaction Types & Directionality:

positive modulator (activating)

potentiator

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Trial Name -

Publications:

Cutrer et al., Attenuation by butalbital of capsaicin-induced c-fos-like immunoreactivity in trigeminal nucleus caudalis., Headache

Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.

Whiting, 2003, The GABAA receptor gene family: new opportunities for drug development., Curr Opin Drug Discov Devel

OLANZAPINE GABRA1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Publications:

Bymaster et al., 1996, Radioreceptor binding profile of the atypical antipsychotic olanzapine., Neuropsychopharmacology

Brafford MV et al., 2014, Olanzapine: an antiemetic option for chemotherapy-induced nausea and vomiting., J Adv Pract Oncol

KETAZOLAM GABRA1

Interaction Types & Directionality:

potentiator

ligand

positive modulator (activating)

Interaction Info:

Publications:

Derry et al., 2004, Identification of a residue in the gamma-aminobutyric acid type A receptor alpha subunit that differentially affects diazepam-sensitive and -insensitive benzodiazepine site binding., J. Neurochem.

Blaschke et al., 1986, [Racemation of the benzodiazepines camazepam and ketazolam and receptor binding of enantiomers]., Arzneimittelforschung

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.

HALOTHANE GABRA1

Interaction Types & Directionality:

positive modulator (activating)

other/unknown

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Publications:

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

Nishikawa K et al., 2002, Volatile anesthetic actions on the GABAA receptors: contrasting effects of alpha 1(S270) and beta 2(N265) point mutations., Neuropharmacology

FLURAZEPAM GABRA1

Interaction Types & Directionality:

potentiator

ligand

positive modulator (activating)

Interaction Info:

Trial Name -

Novel drug target Established target

Publications:

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

PICROTOXIN GABRA1

Interaction Types & Directionality:

blocker (inhibitory)

antagonist (inhibitory)

Interaction Info:

Direct Interaction? True

Endogenous Drug? False

Specific Action of the Ligand None

Publications:

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

PHENOBARBITAL GABRA1

Interaction Types & Directionality:

potentiator

Interaction Info:

Trial Name -

Novel drug target Established target

Publications:

Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.

Whiting, 2003, The GABAA receptor gene family: new opportunities for drug development., Curr Opin Drug Discov Devel

Macdonald et al., 1986, Anticonvulsant drugs: mechanisms of action., Adv Neurol

SECOBARBITAL GABRA1

Interaction Types & Directionality:

potentiator

Interaction Info:

Trial Name -

Novel drug target Established target

Publications:

Peters et al., 1988, Modulation of the GABAA receptor by depressant barbiturates and pregnane steroids., Br. J. Pharmacol.

Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.

Miller et al., 1988, Acute barbiturate administration increases benzodiazepine receptor binding in vivo., Psychopharmacology (Berl.)

NITRAZEPAM GABRA1

Interaction Types & Directionality:

potentiator

ligand

positive modulator (activating)

Interaction Info:

Trial Name -

Novel drug target Established target

Publications:

Podhorna et al., 2000, Behavioural effects of a benzodiazepine receptor partial agonist, Ro 19-8022, in the social conflict test in mice., Behav Pharmacol

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

ETHCHLORVYNOL GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive modulator

Direct Interaction yes

Publications:

Smeyatsky et al., 1992, The treatment of sleep disorders., S. Afr. Med. J.

GLUTETHIMIDE GABRA1

Interaction Types & Directionality:

agonist (activating)

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive modulator

Direct Interaction yes

Publications:

Skerritt et al., 1983, Interactions of some anaesthetic, convulsant, and anticonvulsant drugs at GABA-benzodiazepine receptor-ionophore complexes in rat brain synaptosomal membranes., Neurochem. Res.

BROMAZEPAM GABRA1

Interaction Types & Directionality:

potentiator

ligand

positive modulator (activating)

Interaction Info:

Trial Name -

Novel drug target Established target

Publications:

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem

ACAMPROSATE GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Publications:

Williams, 2005, Medications for treating alcohol dependence., Am Fam Physician

BARBITAL GABRA1

Interaction Types & Directionality:

potentiator

Interaction Info:

Publications:

Whiting, 2003, The GABAA receptor gene family: new opportunities for drug development., Curr Opin Drug Discov Devel

Mehta et al., 1999, An update on GABAA receptors., Brain Res. Brain Res. Rev.

Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.

HEXOBARBITAL GABRA1

Interaction Types & Directionality:

potentiator

Interaction Info:

Novel drug target Established target

Trial Name -

Publications:

Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.

Whiting, 2003, The GABAA receptor gene family: new opportunities for drug development., Curr Opin Drug Discov Devel

Mehta et al., 1999, An update on GABAA receptors., Brain Res. Brain Res. Rev.

LORAZEPAM GABRA1

Interaction Types & Directionality:

positive modulator (activating)

ligand

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Trial Name -

Publications:

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem

BUTETHAL GABRA1

Interaction Types & Directionality:

potentiator

Interaction Info:

Trial Name -

Novel drug target Established target

Publications:

Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.

Whiting, 2003, The GABAA receptor gene family: new opportunities for drug development., Curr Opin Drug Discov Devel

Mehta et al., 1999, An update on GABAA receptors., Brain Res. Brain Res. Rev.

ALCOHOL GABRA1

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Publications:

Earl et al., 2011, Inhibition of recombinant L-type voltage-gated calcium channels by positive allosteric modulators of GABAA receptors., J. Pharmacol. Exp. Ther.

Davies, 2003, The role of GABAA receptors in mediating the effects of alcohol in the central nervous system., J Psychiatry Neurosci

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

APROBARBITAL GABRA1

Interaction Types & Directionality:

potentiator

Interaction Info:

Publications:

Whiting, 2003, The GABAA receptor gene family: new opportunities for drug development., Curr Opin Drug Discov Devel

Mehta et al., 1999, An update on GABAA receptors., Brain Res. Brain Res. Rev.

Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.

THIOCOLCHICOSIDE GABRA1

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Publications:

Carta et al., 2006, The muscle relaxant thiocolchicoside is an antagonist of GABAA receptor function in the central nervous system., Neuropharmacology

Mascia et al., 2007, Thiocolchicoside inhibits the activity of various subtypes of recombinant GABA(A) receptors expressed in Xenopus laevis oocytes., Eur. J. Pharmacol.

AMOBARBITAL GABRA1

Interaction Types & Directionality:

potentiator

Interaction Info:

Publications:

Whiting, 2003, The GABAA receptor gene family: new opportunities for drug development., Curr Opin Drug Discov Devel

Mehta et al., 1999, An update on GABAA receptors., Brain Res. Brain Res. Rev.

Yamakura et al., 2001, Anesthetics and ion channels: molecular models and sites of action., Annu. Rev. Pharmacol. Toxicol.

PRASTERONE GABRA1

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Publications:

Sousa et al., 1997, Interactions of the neurosteroid dehydroepiandrosterone sulfate with the GABA(A) receptor complex reveals that it may act via the picrotoxin site., J. Pharmacol. Exp. Ther.

FLUNITRAZEPAM GABRA1

Interaction Types & Directionality:

allosteric modulator

ligand

positive modulator (activating)

Interaction Info:

Specific Binding Site for Interaction benzodiazepine site

Details of the Assay for Interaction Assay using recombinant GABAA channels with subunit composition; α1β3γ2.

Specific Action of the Ligand Positive

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem

LOPRAZOLAM GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem

LAMOTRIGINE GABRA1

Interaction Types & Directionality:

inducer (activating)

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Publications:

Braga MF et al., 2002, Lamotrigine reduces spontaneous and evoked GABAA receptor-mediated synaptic transmission in the basolateral amygdala: implications for its effects in seizure and affective disorders., Neuropharmacology

Wang JF et al., 2002, Lamotrigine increases gene expression of GABA-A receptor beta3 subunit in primary cultured rat hippocampus cells., Neuropsychopharmacology

Abelaira HM et al., 2012, Lamotrigine treatment reverses depressive-like behavior and alters BDNF levels in the brains of maternally deprived adult rats., Pharmacol Biochem Behav

BENZODIAZEPINE GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem

MEMANTINE GABRA1

Interaction Types & Directionality:

binder

Interaction Info:

Publications:

Molinaro G et al., 2009, Memantine treatment reduces the expression of the K(+)/Cl(-) cotransporter KCC2 in the hippocampus and cerebral cortex, and attenuates behavioural responses mediated by GABA(A) receptor activation in mice., Brain Res

MEXAZOLAM GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem

Fernandes H et al., 2014, Mexazolam: clinical efficacy and tolerability in the treatment of anxiety., Neurol Ther

TAURINE GABRA1

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Publications:

Kilb W et al., 2017, Taurine as an Essential Neuromodulator during Perinatal Cortical Development., Front Cell Neurosci
DELORAZEPAM GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem
LORMETAZEPAM GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature
DOXEFAZEPAM GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem
CLOXAZOLAM GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem
ETIZOLAM GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem
MEDAZEPAM GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem
ETHYL LOFLAZEPATE GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem
CINAZEPAM GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem
CAMAZEPAM GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem
BENTAZEPAM GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem
APALUTAMIDE GABRA1

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Publications:

Clegg NJ et al., 2012, ARN-509: a novel antiandrogen for prostate cancer treatment., Cancer Res

CARISOPRODOL GABRA1

Interaction Types & Directionality:

modulator

activator (activating)

Interaction Info:

Publications:

Gonzalez LA et al., 2009, Abuse Potential of Soma: the GABA(A) Receptor as a Target., Mol Cell Pharmacol

Gonzalez et al., 2009, Carisoprodol-mediated modulation of GABAA receptors: in vitro and in vivo studies., J. Pharmacol. Exp. Ther.

Kumar M et al., 2016, Assessment of direct gating and allosteric modulatory effects of meprobamate in recombinant GABA(A) receptors., Eur J Pharmacol

PINAZEPAM GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem
STIRIPENTOL GABRA1

Interaction Types & Directionality:

agonist (activating)

positive modulator (activating)

Interaction Info:

Publications:

Fisher JL, 2009, The anti-convulsant stiripentol acts directly on the GABA(A) receptor as a positive allosteric modulator., Neuropharmacology
NORDAZEPAM GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem
BROTIZOLAM GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem
CHEMBL146245 GABRA1

Interaction Types & Directionality:

ligand

positive modulator (activating)

Interaction Info:

Publications:

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature
CHEMBL488994 GABRA1

Interaction Types & Directionality:

ligand

Interaction Info:

Publications:

Huen MS et al., 2003, Naturally occurring 2'-hydroxyl-substituted flavonoids as high-affinity benzodiazepine site ligands., Biochem Pharmacol
BREXANOLONE GABRA1

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Publications:
REMIMAZOLAM GABRA1

Interaction Types & Directionality:

n/a

Interaction Info:

Trial Name CNS-7056

Novel drug target Established target

Publications:
ACAMPROSATE CALCIUM GABRA1

Interaction Types & Directionality:

n/a

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive modulator

Direct Interaction yes

Publications:
GANAXOLONE GABRA1

Interaction Types & Directionality:

n/a

Interaction Info:

Trial Name Ganaxolone

Novel drug target Established target

Publications:
TRICLOFOS SODIUM GABRA1

Interaction Types & Directionality:

n/a

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive modulator

Direct Interaction yes

Publications:

CARBAMAZEPINE GABRA1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Zhou BT et al., 2012, Effects of SCN1A and GABA receptor genetic polymorphisms on carbamazepine tolerability and efficacy in Chinese patients with partial seizures: 2-year longitudinal clinical follow-up., CNS Neurosci Ther

SANDARACOPIMARIC ACID GABRA1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Zaugg J et al., 2011, Identification and characterization of GABA(A) receptor modulatory diterpenes from Biota orientalis that decrease locomotor activity in mice., J Nat Prod
ISONIPECOTIC ACID GABRA1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Petersen JG et al., 2014, Synthesis and pharmacological evaluation of 6-aminonicotinic acid analogues as novel GABA(A) receptor agonists., Eur J Med Chem
PHENYTOIN GABRA1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Keppel Hesselink JM, 2017, Phenytoin: a step by step insight into its multiple mechanisms of action-80 years of mechanistic studies in neuropharmacology., J Neurol
ISOPIMARIC ACID GABRA1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Zaugg J et al., 2011, Identification and characterization of GABA(A) receptor modulatory diterpenes from Biota orientalis that decrease locomotor activity in mice., J Nat Prod

AZIETOMIDATE GABRA1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Husain SS et al., 2006, Synthesis of trifluoromethylaryl diazirine and benzophenone derivatives of etomidate that are potent general anesthetics and effective photolabels for probing sites on ligand-gated ion channels., J Med Chem

CHEMBL2170369 GABRA1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Anzini M et al., 2011, New insight into the central benzodiazepine receptor-ligand interactions: design, synthesis, biological evaluation, and molecular modeling of 3-substituted 6-phenyl-4H-imidazo[1,5-a][1,4]benzodiazepines and related compounds., J Med Chem

CHEMBL1518572 GABRA1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
CLOMETHIAZOLE GABRA1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Ensembl: ENSG00000022355
- Version: 101_38
Alternate Names:

GABRA1 Ensembl Gene Name

Gene Info:

Gene Biotype PROTEIN_CODING

Publications:
RussLampel: ENSG00000022355
- Version: 26-July-2011
Alternate Names:

GAMMA-AMINOBUTYRIC-ACID RECEPTOR ALPHA-1 SUBUNIT PRECURSOR (GABA(A) RECEPTOR). [SOURCE:UNIPROT/SWISSPROT;ACC:P14867] Description

GABRA1 Display Id

ENSG00000022355 Ensembl Gene Id

Gene Info:

Human Readable Name DRUGGABLE GENOME

Gene Categories:

DRUGGABLE GENOME

Publications:
TEND: P14867
- Version: 01-August-2011
Alternate Names:

2554 Entrez Gene Id

GBRA1_HUMAN Uniprot Id

ENSG00000022355 Ensembl Gene Id

Gene Info:

Target Subclass Channels

Target Subclass Ligand_gated_ion_channels

Target Subclass cys-loop

Publications:
HopkinsGroom: P14867
- Version: 11-September-2012
Alternate Names:

ENSG00000022355 Ensembl Gene Id

GAMMA-AMINOBUTYRIC ACID RECEPTOR SUBUNIT ALPHA-1 Uniprot Protein Name

2554 Entrez Gene Id

Gene Info:

Human Readable Name ION CHANNEL

Interpro Short Name Neur_chan_lig-bd

Human Readable Name DRUGGABLE GENOME

Gene Categories:

ION CHANNEL, DRUGGABLE GENOME

Publications:
TdgClinicalTrial: P14867
- Version: January-2014
Alternate Names:

GABRA1 Gene Symbol

GABRD Gene Symbol

Gene Info:

Target Class Receptors

Target Subclass TC:1.A.9

Publications:
GuideToPharmacology: 2554
- Version: 29-September-2020
Alternate Names:

4075 HUGO Gene ID

4075 HUGO Gene Symbol

gamma-aminobutyric acid type A receptor subunit alpha1 HUGO Gene Name

Gene Info:

GuideToPharmacology Gene Category Name GABAA receptors

GuideToPharmacology Gene Category ID 72

Gene Categories:

ION CHANNEL

Publications:

PharmGKB: GABRA1

Version: 18-August-2020

Alternate Names:

PA28489 PharmGKB ID

Gene Info:

Publications:

Zhou BT et al., 2012, Effects of SCN1A and GABA receptor genetic polymorphisms on carbamazepine tolerability and efficacy in Chinese patients with partial seizures: 2-year longitudinal clinical follow-up., CNS Neurosci Ther

DrugBank: BE0000795

Version: 5.1.7

Alternate Names:

GABRA1 DrugBank Gene Name

P14867 UniProt Accession

2554 Entrez Gene Id

Gene Info:

Publications:

Krasowski et al., 1999, General anaesthetic actions on ligand-gated ion channels., Cell. Mol. Life Sci.

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

DrugBank: BE0004797

Version: 5.1.7

Alternate Names:

GABRA1 DrugBank Gene Name

P14867 UniProt Accession

2554 Entrez Gene Id

Gene Info:

Publications:

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

DrugBank: BE0008668

Version: 5.1.7

Alternate Names:

GABRA1 DrugBank Gene Name

P14867 UniProt Accession

2554 Entrez Gene Id

Gene Info:

Publications:

Sigel E et al., 2012, Structure, function, and modulation of GABA(A) receptors., J Biol Chem

Zhu S et al., 2018, Structure of a human synaptic GABAA receptor., Nature

Brafford MV et al., 2014, Olanzapine: an antiemetic option for chemotherapy-induced nausea and vomiting., J Adv Pract Oncol

DTC: GABRA1

Version: 02-September-2020

Alternate Names:

Gene Info:

Publications:

Husain SS et al., 2006, Synthesis of trifluoromethylaryl diazirine and benzophenone derivatives of etomidate that are potent general anesthetics and effective photolabels for probing sites on ligand-gated ion channels., J Med Chem

Anzini M et al., 2011, New insight into the central benzodiazepine receptor-ligand interactions: design, synthesis, biological evaluation, and molecular modeling of 3-substituted 6-phenyl-4H-imidazo[1,5-a][1,4]benzodiazepines and related compounds., J Med Chem

Zaugg J et al., 2011, Identification and characterization of GABA(A) receptor modulatory diterpenes from Biota orientalis that decrease locomotor activity in mice., J Nat Prod

HingoraniCasas: ENSG00000022355
- Version: 31-May-2017
Alternate Names:

ENSG00000022355 Gene Symbol

GABRA1 Ensembl Id

Gene Info:

Gene Categories:

DRUGGABLE GENOME

Publications:
ChemblInteractions: GABRA1
- Version: chembl_23
Alternate Names:

GABRA1 GENE_SYMBOL

Gamma-aminobutyric acid receptor subunit alpha-1 UNIPROT

GABA(A) receptor subunit alpha-1 UNIPROT

Gene Info:

Publications:
Pharos: GABRA1
- Version: 03-September-2020
Alternate Names:

Gamma-aminobutyric acid receptor subunit alpha-1 Gene Name

P14867 UniProt ID

Gene Info:

Gene Categories:

ION CHANNEL

Publications:
TTD: GABA(A) receptor alpha-1
- Version: 2020.06.01
Alternate Names:

GABRA1 TTD Gene Abbreviation

T51487 TTD Target ID

Gene Info:

Publications:

Trial Name	JZP-8
Novel drug target	Established target
Details of the Assay for Interaction	Assay using recombinant GABA<sub>A</sub> channels with subunit composition; α1β1γ2.

Direct Interaction	yes
Mechanism of Interaction	GABA-A receptor; anion channel positive allosteric modulator
Specific Binding Site for Interaction	benzodiazepine site

Specific Binding Site for Interaction	GABA site
Specific Action of the Ligand	Antagonist
Endogenous Drug?	False

Direct Interaction?	True
Endogenous Drug?	False
Specific Action of the Ligand	Positive

Trial Name	NG2-73
Novel drug target	Established target
Direct Interaction	yes

Mechanism of Interaction	GABA receptor alpha-1 subunit positive allosteric modulator
Direct Interaction	yes
Trial Name	Indiplon

Direct Interaction	yes
Mechanism of Interaction	GABA-A receptor; benzodiazepine site positive allosteric modulator

Mechanism of Interaction	GABA A receptor alpha-1/beta-1/gamma-2 positive allosteric modulator
Direct Interaction	yes

Mechanism of Interaction	GABA-A receptor; anion channel agonist
Direct Interaction	yes

Mechanism of Interaction	GABA-A receptor; agonist GABA site agonist
Direct Interaction	yes
Specific Binding Site for Interaction	GABA site

Trial Name	ocinaplon
Novel drug target	Established target
Specific Binding Site for Interaction	benzodiazepine site

Mechanism of Interaction	GABA-A receptor; benzodiazepine site inverse agonist
Direct Interaction	yes

GAMMA-AMINOBUTYRIC-ACID RECEPTOR ALPHA-1 SUBUNIT PRECURSOR (GABA(A) RECEPTOR). [SOURCE:UNIPROT/SWISSPROT;ACC:P14867]	Description
GABRA1	Display Id
ENSG00000022355	Ensembl Gene Id

2554	Entrez Gene Id
GBRA1_HUMAN	Uniprot Id
ENSG00000022355	Ensembl Gene Id

4075	HUGO Gene ID
4075	HUGO Gene Symbol
gamma-aminobutyric acid type A receptor subunit alpha1	HUGO Gene Name

GABRA1	DrugBank Gene Name
P14867	UniProt Accession
2554	Entrez Gene Id

GABRA1	GENE_SYMBOL
Gamma-aminobutyric acid receptor subunit alpha-1	UNIPROT
GABA(A) receptor subunit alpha-1	UNIPROT

Gamma-aminobutyric acid receptor subunit alpha-1	Gene Name
P14867	UniProt ID

GABRA1 Gene Record

GABRA1 2554 Druggable Genome

Alternate Names:

Gene Info:

Gene Categories: Category Details

Publications:

Interaction Types & Directionality: allosteric modulator positive modulator (activating) ligand

Interaction Info: Trial Name JZP-8 Novel drug target Established target Details of the Assay for Interaction Assay using recombinant GABA<sub>A</sub> channels with subunit composition; &alpha;1&beta;1&gamma;2.

Publications: Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther. Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand. Zhu S et al., 2018, Structure of a human synaptic GABA<sub>A</sub> receptor., Nature

Interaction Types & Directionality: positive modulator (activating) allosteric modulator ligand

Interaction Info: Direct Interaction yes Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator Specific Binding Site for Interaction benzodiazepine site

Interaction Types & Directionality: potentiator positive modulator (activating) allosteric modulator

Interaction Info: Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator Direct Interaction yes Trial Name ARX-03, sufentanil + triazolam NanoTab

Publications: Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther. Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand. Zhu S et al., 2018, Structure of a human synaptic GABA<sub>A</sub> receptor., Nature

Interaction Types & Directionality: positive modulator (activating)

Interaction Info: Trial Name - Novel drug target Established target Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Publications: Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther. Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Interaction Types & Directionality: antagonist (inhibitory) allosteric modulator positive modulator (activating)

Interaction Info: Specific Binding Site for Interaction benzodiazepine site Details of the Assay for Interaction Affinity measured using &alpha;1&beta;3&gamma;2 receptors. Specific Action of the Ligand Antagonist

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Specific Binding Site for Interaction GABA site Specific Action of the Ligand Antagonist Endogenous Drug? False

Publications: Qi ZH et al., 2007, Protein kinase C epsilon regulates gamma-aminobutyrate type A receptor sensitivity to ethanol and benzodiazepines through phosphorylation of gamma2 subunits., J Biol Chem

Interaction Types & Directionality: allosteric modulator potentiator positive modulator (activating)

Interaction Info: Direct Interaction? True Endogenous Drug? False Specific Action of the Ligand Positive

Interaction Types & Directionality: agonist (activating)

Interaction Info: Direct Interaction? False Endogenous Drug? False Specific Action of the Ligand Full agonist

Publications: Stewart DS et al., 2011, p-(4-Azipentyl)propofol: a potent photoreactive general anesthetic derivative of propofol., J Med Chem

Interaction Types & Directionality: positive modulator (activating)

Interaction Info: Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator Direct Interaction yes

Publications:

Interaction Types & Directionality: agonist (activating)

Interaction Info: Specific Binding Site for Interaction GABA site Specific Action of the Ligand Full agonist Endogenous Drug? False

Publications:

Interaction Types & Directionality: partial agonist (activating)

Interaction Info: Trial Name NG2-73 Novel drug target Established target Direct Interaction yes

Publications:

Interaction Types & Directionality: positive modulator (activating)

Interaction Info: Direct Interaction yes Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Publications:

Interaction Types & Directionality: positive modulator (activating) allosteric modulator

Interaction Info: Mechanism of Interaction GABA receptor alpha-1 subunit positive allosteric modulator Direct Interaction yes Trial Name Indiplon

Publications:

Interaction Types & Directionality: allosteric modulator

Interaction Info: Specific Binding Site for Interaction benzodiazepine site Specific Action of the Ligand Full agonist Endogenous Drug? False

Publications:

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Specific Binding Site for Interaction GABA site Specific Action of the Ligand Antagonist Endogenous Drug? False

Publications:

Interaction Types & Directionality: positive modulator (activating)

Interaction Info: Direct Interaction yes Mechanism of Interaction GABA-A receptor; benzodiazepine site positive allosteric modulator

Publications:

Interaction Types & Directionality: positive modulator (activating)

Interaction Info: Mechanism of Interaction GABA A receptor alpha-1/beta-1/gamma-2 positive allosteric modulator Direct Interaction yes

Publications:

Interaction Types & Directionality: positive modulator (activating)

Interaction Info: Direct Interaction yes Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Publications:

Interaction Types & Directionality: agonist (activating)

Interaction Info: Mechanism of Interaction GABA-A receptor; anion channel agonist Direct Interaction yes

Publications:

Interaction Types & Directionality: agonist (activating)

Interaction Info: Mechanism of Interaction GABA-A receptor; agonist GABA site agonist Direct Interaction yes Specific Binding Site for Interaction GABA site

Publications:

Interaction Types & Directionality: positive modulator (activating)

Interaction Info: Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator Direct Interaction yes

Publications:

Interaction Types & Directionality: allosteric modulator

Interaction Info: Trial Name ocinaplon Novel drug target Established target Specific Binding Site for Interaction benzodiazepine site

Publications:

Interaction Types & Directionality: positive modulator (activating)

Interaction Info: Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator Direct Interaction yes

Publications:

Interaction Types & Directionality: positive modulator (activating)

Interaction Info: Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator Direct Interaction yes

Publications:

Interaction Types & Directionality: inverse agonist (inhibitory)

Interaction Info: Mechanism of Interaction GABA-A receptor; benzodiazepine site inverse agonist Direct Interaction yes

Publications:

Interaction Types & Directionality: positive modulator (activating)

Interaction Info: Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator Direct Interaction yes

Interaction Types & Directionality:

allosteric modulator

positive modulator (activating)

ligand

Interaction Info:

Trial Name JZP-8

Novel drug target Established target

Details of the Assay for Interaction Assay using recombinant GABA<sub>A</sub> channels with subunit composition; α1β1γ2.

Publications:

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Zhu S et al., 2018, Structure of a human synaptic GABA<sub>A</sub> receptor., Nature

Interaction Types & Directionality:

positive modulator (activating)

allosteric modulator

ligand

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Specific Binding Site for Interaction benzodiazepine site

Interaction Types & Directionality:

potentiator

positive modulator (activating)

allosteric modulator

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Trial Name ARX-03, sufentanil + triazolam NanoTab

Publications:

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Zhu S et al., 2018, Structure of a human synaptic GABA<sub>A</sub> receptor., Nature

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Trial Name -

Novel drug target Established target

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Publications:

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Interaction Types & Directionality:

antagonist (inhibitory)

allosteric modulator

positive modulator (activating)

Interaction Info:

Specific Binding Site for Interaction benzodiazepine site

Details of the Assay for Interaction Affinity measured using α1β3γ2 receptors.

Specific Action of the Ligand Antagonist

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Binding Site for Interaction GABA site

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Publications:

Qi ZH et al., 2007, Protein kinase C epsilon regulates gamma-aminobutyrate type A receptor sensitivity to ethanol and benzodiazepines through phosphorylation of gamma2 subunits., J Biol Chem

Interaction Types & Directionality:

allosteric modulator

potentiator

positive modulator (activating)

Interaction Info:

Direct Interaction? True

Endogenous Drug? False

Specific Action of the Ligand Positive

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Full agonist

Publications:

Stewart DS et al., 2011, p-(4-Azipentyl)propofol: a potent photoreactive general anesthetic derivative of propofol., J Med Chem

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Specific Binding Site for Interaction GABA site

Specific Action of the Ligand Full agonist

Endogenous Drug? False

Interaction Types & Directionality:

partial agonist (activating)

Interaction Info:

Trial Name NG2-73

Novel drug target Established target

Direct Interaction yes

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Interaction Types & Directionality:

positive modulator (activating)

allosteric modulator

Interaction Info:

Mechanism of Interaction GABA receptor alpha-1 subunit positive allosteric modulator

Direct Interaction yes

Trial Name Indiplon

Interaction Types & Directionality:

allosteric modulator

Interaction Info:

Specific Binding Site for Interaction benzodiazepine site

Specific Action of the Ligand Full agonist

Endogenous Drug? False

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Binding Site for Interaction GABA site

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; benzodiazepine site positive allosteric modulator

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA A receptor alpha-1/beta-1/gamma-2 positive allosteric modulator

Direct Interaction yes

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel agonist

Direct Interaction yes

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; agonist GABA site agonist

Direct Interaction yes

Specific Binding Site for Interaction GABA site

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Interaction Types & Directionality:

allosteric modulator

Interaction Info:

Trial Name ocinaplon

Novel drug target Established target

Specific Binding Site for Interaction benzodiazepine site

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Interaction Types & Directionality:

inverse agonist (inhibitory)

Interaction Info:

Mechanism of Interaction GABA-A receptor; benzodiazepine site inverse agonist

Direct Interaction yes

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Interaction Types & Directionality:

allosteric modulator

Interaction Info:

Specific Binding Site for Interaction benzodiazepine site

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Direct Interaction yes

Interaction Types & Directionality:

positive modulator (activating)

potentiator

Interaction Info:

Direct Interaction yes

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Trial Name -

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

Interaction Types & Directionality:

positive modulator (activating)

Interaction Info:

Trial Name -

Novel drug target Established target

Publications:

Möhler et al., 2002, A new benzodiazepine pharmacology., J. Pharmacol. Exp. Ther.

Riss et al., 2008, Benzodiazepines in epilepsy: pharmacology and pharmacokinetics., Acta Neurol. Scand.

Interaction Types & Directionality:

agonist (activating)

positive modulator (activating)

Interaction Info:

Trial Name -

Novel drug target Established target

Mechanism of Interaction GABA-A receptor; anion channel positive allosteric modulator

Interaction Types & Directionality:

agonist (activating)

positive modulator (activating)

Interaction Info:

Mechanism of Interaction GABA-A receptor; anion channel positive modulator

Direct Interaction yes

Trial Name topiramate controlled release,Trokesa

Interaction Types & Directionality:

antagonist (inhibitory)

binder