Tmic
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2009-07-21 20:26:52 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2787
Identification
Common NameZolpidem
ClassSmall Molecule
DescriptionZolpidem (sold under the brand names Ambien, Ambien CR, Stilnox, and Sublinox) is a prescription medication used for the treatment of insomnia, as well as some brain disorders. It is a short-acting nonbenzodiazepine hypnotic of the imidazopyridine class that potentiates gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, by binding to GABAA receptors at the same location as benzodiazepines. It works quickly (usually within 15 minutes) and has a short half-life (two to three hours). Zolpidem has not adequately demonstrated effectiveness in maintaining sleep (unless delivered in a controlled-release form); however, it is effective in initiating sleep. Some users take zolpidem recreationally for these side effects. However, it may be less common than benzodiazepine abuse. Zolpidem can become addictive if taken for extended periods of time, due to dependence on its ability to put one to sleep or to the euphoria it can sometimes produce.
Compound Type
  • Amide
  • Amine
  • Drug
  • Food Toxin
  • GABA Agonist
  • GABA-A Receptor Agonist
  • Hypnotic and Sedative
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Adormix
Ambien
Ambien CR
Bikalm
Dormizol
Edluar
Hypnogen
Intermezzo
Ivadal
Ivedal
Myslee
N,N,6-Trimethyl-2-(4-methylphenyl)imidazo(1,2-a)pyridine-3-acetamide
Nasen
Nimadorm
Nottem
Stilnoct
Stilnox
Stilnox CR
Zolpidem Ambien
Zolpidem tartrate
Zolpidemum
Zolpimist
Zolsana
Zoltis
Chemical FormulaC19H21N3O
Average Molecular Mass307.390 g/mol
Monoisotopic Mass307.168 g/mol
CAS Registry Number82626-48-0
IUPAC NameN,N-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide
Traditional Namezolpidem
SMILESCN(C)C(=O)CC1=C(N=C2C=CC(C)=CN12)C1=CC=C(C)C=C1
InChI IdentifierInChI=1S/C19H21N3O/c1-13-5-8-15(9-6-13)19-16(11-18(23)21(3)4)22-12-14(2)7-10-17(22)20-19/h5-10,12H,11H2,1-4H3
InChI KeyInChIKey=ZAFYATHCZYHLPB-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenylimidazoles. These are polycyclic aromatic compounds containing a benzene ring linked to an imidazole ring through a CC or CN bond.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzoles
Sub ClassImidazoles
Direct ParentPhenylimidazoles
Alternative Parents
Substituents
  • 5-phenylimidazole
  • 4-phenylimidazole
  • Imidazopyridine
  • Imidazo[1,2-a]pyridine
  • Toluene
  • Methylpyridine
  • Monocyclic benzene moiety
  • N-substituted imidazole
  • Pyridine
  • Benzenoid
  • Tertiary carboxylic acid amide
  • Heteroaromatic compound
  • Carboxamide group
  • Carboxylic acid derivative
  • Azacycle
  • Organic oxide
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxygen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Liver
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point196°C
Boiling PointNot Available
Solubility23 mg/mL
LogP1.2
Predicted Properties
PropertyValueSource
Water Solubility0.031 g/LALOGPS
logP3.15ALOGPS
logP3.02ChemAxon
logS-4ALOGPS
pKa (Strongest Basic)5.65ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area37.61 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity93.58 m³·mol⁻¹ChemAxon
Polarizability35.06 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-007c-4491000000-1f69c88ada0cbe422976View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4r-0196000000-6304f5b37ed9f071eb26View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0049000000-bc33df0258d99c887a5cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0bti-0095000000-53d24c4b41c278d039e0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052r-1190000000-fcb2a47c2fab91af9648View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0009000000-ad3531d27ad6da8d9cc3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0bt9-1097000000-084e5a788c15061e05a5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-08fs-2090000000-b2e3eaa1af64958efe10View in MoNA
MSMass Spectrum (Electron Ionization)splash10-000i-1090000000-5429f5620534a2340098View in MoNA
Toxicity Profile
Route of ExposureOral. Zolpidem is rapidly absorbed from the GI tract.
Mechanism of ToxicityZolpidem modulates the alpha-subunit, known as the benzodiazepine receptor, within the GABAA receptor chloride channel macromolecular complex. Unlike the benzodiazepines, which non-selectively interact with all three alpha-receptor subtypes, Zolpidem preferentially binds to the alpha-1 receptor.
MetabolismZolpidem is converted to inactive metabolites in the liver. Route of Elimination: Zolpidem tartrate tablets are converted to inactive metabolites that are eliminated primarily by renal excretion. Half Life: 2.6 hours
Toxicity ValuesLD50: 695 mg/kg (Oral, Rat) (6)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the short-term treatment of insomnia.
Minimum Risk LevelNot Available
Health EffectsThey cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive.
SymptomsSymptoms of overdose include impairment of consciousness ranging from somnolence to light coma.
TreatmentGeneral symptomatic and supportive measures should be used along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. sedative hypnotic effect was shown to be reduced by flumazenil and therefore may be useful; however, flumazenil administration may contribute to the appearance of neurological symptoms (convulsions). As in all cases of drug overdose, respiration, pulse, blood pressure, and other appropriate signs should be monitored and general supportive measures employed. Hypotension and CNS depression should be monitored and treated by appropriate medical intervention. Sedating drugs should be withheld following zolpidem overdosage, even if excitation occurs. The value of dialysis in the treatment of overdosage has not been determined, although hemodialysis studies in patients with renal failure receiving therapeutic doses have demonstrated that zolpidem is not dialyzable. (11)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00425
HMDB IDHMDB05023
PubChem Compound ID5732
ChEMBL IDCHEMBL911
ChemSpider ID5530
KEGG IDC07219
UniProt IDNot Available
OMIM ID
ChEBI ID10125
BioCyc IDNot Available
CTD IDNot Available
Stitch IDZolpidem
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkZolpidem
References
Synthesis Reference

Markus Sauter, “Process for preparing zolpidem.” U.S. Patent US20020183522, issued December 05, 2002.

MSDSLink
General References
  1. Lemmer B: The sleep-wake cycle and sleeping pills. Physiol Behav. 2007 Feb 28;90(2-3):285-93. Epub 2006 Oct 16. [17049955 ]
  2. Depoortere H, Zivkovic B, Lloyd KG, Sanger DJ, Perrault G, Langer SZ, Bartholini G: Zolpidem, a novel nonbenzodiazepine hypnotic. I. Neuropharmacological and behavioral effects. J Pharmacol Exp Ther. 1986 May;237(2):649-58. [2871178 ]
  3. Clauss RP, Guldenpfennig WM, Nel HW, Sathekge MM, Venkannagari RR: Extraordinary arousal from semi-comatose state on zolpidem. A case report. S Afr Med J. 2000 Jan;90(1):68-72. [10721397 ]
  4. Schlich D, L'Heritier C, Coquelin JP, Attali P, Kryrein HJ: Long-term treatment of insomnia with zolpidem: a multicentre general practitioner study of 107 patients. J Int Med Res. 1991 May-Jun;19(3):271-9. [1670039 ]
  5. Maarek L, Cramer P, Attali P, Coquelin JP, Morselli PL: The safety and efficacy of zolpidem in insomniac patients: a long-term open study in general practice. J Int Med Res. 1992 Apr;20(2):162-70. [1521672 ]
  6. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  7. Gock SB, Wong SH, Nuwayhid N, Venuti SE, Kelley PD, Teggatz JR, Jentzen JM: Acute zolpidem overdose--report of two cases. J Anal Toxicol. 1999 Oct;23(6):559-62. [10517569 ]
  8. Von Moltke LL, Greenblatt DJ, Granda BW, Duan SX, Grassi JM, Venkatakrishnan K, Harmatz JS, Shader RI: Zolpidem metabolism in vitro: responsible cytochromes, chemical inhibitors, and in vivo correlations. Br J Clin Pharmacol. 1999 Jul;48(1):89-97. [10383565 ]
  9. von Moltke LL, Weemhoff JL, Perloff MD, Hesse LM, Harmatz JS, Roth-Schechter BF, Greenblatt DJ: Effect of zolpidem on human cytochrome P450 activity, and on transport mediated by P-glycoprotein. Biopharm Drug Dispos. 2002 Dec;23(9):361-7. [12469329 ]
  10. Drugs.com [Link]
  11. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA3
Uniprot ID:
P34903
Molecular Weight:
55164.055 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.246 uMNot AvailableBindingDB 26266
Inhibitory0.38 uMNot AvailableBindingDB 26266
Inhibitory0.383 uMNot AvailableBindingDB 26266
Inhibitory0.6085 uMNot AvailableBindingDB 26266
Inhibitory1.85 uMNot AvailableBindingDB 26266
Inhibitory2.1495 uMNot AvailableBindingDB 26266
References
  1. Pritchett DB, Seeburg PH: Gamma-aminobutyric acidA receptor alpha 5-subunit creates novel type II benzodiazepine receptor pharmacology. J Neurochem. 1990 May;54(5):1802-4. [2157817 ]
  2. Smith AJ, Alder L, Silk J, Adkins C, Fletcher AE, Scales T, Kerby J, Marshall G, Wafford KA, McKernan RM, Atack JR: 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. 2001 May;59(5):1108-18. [11306694 ]
  3. Russell MG, Carling RW, Atack JR, Bromidge FA, Cook SM, Hunt P, Isted C, Lucas M, McKernan RM, Mitchinson A, Moore KW, Narquizian R, Macaulay AJ, Thomas D, Thompson SA, Wafford KA, Castro JL: Discovery of functionally selective 7,8,9,10-tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazines as GABA A receptor agonists at the alpha3 subunit. J Med Chem. 2005 Mar 10;48(5):1367-83. [15743180 ]
  4. Carling RW, Moore KW, Street LJ, Wild D, Isted C, Leeson PD, Thomas S, O'Connor D, McKernan RM, Quirk K, Cook SM, Atack JR, Wafford KA, Thompson SA, Dawson GR, Ferris P, Castro JL: 3-phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-a]phthalazines and analogues: high-affinity gamma-aminobutyric acid-A benzodiazepine receptor ligands with alpha 2, alpha 3, and alpha 5-subtype binding selectivity over alpha 1. J Med Chem. 2004 Mar 25;47(7):1807-22. [15027873 ]
  5. Carling RW, Madin A, Guiblin A, Russell MG, Moore KW, Mitchinson A, Sohal B, Pike A, Cook SM, Ragan IC, McKernan RM, Quirk K, Ferris P, Marshall G, Thompson SA, Wafford KA, Dawson GR, Atack JR, Harrison T, Castro JL, Street LJ: 7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl) -1,2,4-triazolo[4,3-b]pyridazine: a functionally selective gamma-aminobutyric acid(A) (GABA(A)) alpha2/alpha3-subtype selective agonist that exhibits potent anxiolytic activity but is not sedating in animal models. J Med Chem. 2005 Nov 17;48(23):7089-92. [16279764 ]
  6. Cox ED, Diaz-Arauzo H, Huang Q, Reddy MS, Ma C, Harris B, McKernan R, Skolnick P, Cook JM: Synthesis and evaluation of analogues of the partial agonist 6-(propyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (6-PBC) and the full agonist 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (Zk 93423) at wild type and recombinant GABAA receptors. J Med Chem. 1998 Jul 2;41(14):2537-52. [9651158 ]
  7. Yin W, Majumder S, Clayton T, Petrou S, VanLinn ML, Namjoshi OA, Ma C, Cromer BA, Roth BL, Platt DM, Cook JM: Design, synthesis, and subtype selectivity of 3,6-disubstituted beta-carbolines at Bz/GABA(A)ergic receptors. SAR and studies directed toward agents for treatment of alcohol abuse. Bioorg Med Chem. 2010 Nov 1;18(21):7548-64. doi: 10.1016/j.bmc.2010.08.049. Epub 2010 Sep 29. [20888240 ]
  8. Street LJ, Sternfeld F, Jelley RA, Reeve AJ, Carling RW, Moore KW, McKernan RM, Sohal B, Cook S, Pike A, Dawson GR, Bromidge FA, Wafford KA, Seabrook GR, Thompson SA, Marshall G, Pillai GV, Castro JL, Atack JR, MacLeod AM: Synthesis and biological evaluation of 3-heterocyclyl-7,8,9,10-tetrahydro-(7,10-ethano)-1,2,4-triazolo[3,4-a]phthalazine s and analogues as subtype-selective inverse agonists for the GABA(A)alpha5 benzodiazepine binding site. J Med Chem. 2004 Jul 1;47(14):3642-57. [15214791 ]
  9. Lager E, Andersson P, Nilsson J, Pettersson I, Nielsen EO, Nielsen M, Sterner O, Liljefors T: 4-quinolone derivatives: high-affinity ligands at the benzodiazepine site of brain GABA A receptors. synthesis, pharmacology, and pharmacophore modeling. J Med Chem. 2006 Apr 20;49(8):2526-33. [16610795 ]
  10. Hadingham KL, Wingrove P, Le Bourdelles B, Palmer KJ, Ragan CI, Whiting PJ: Cloning of cDNA sequences encoding human alpha 2 and alpha 3 gamma-aminobutyric acidA receptor subunits and characterization of the benzodiazepine pharmacology of recombinant alpha 1-, alpha 2-, alpha 3-, and alpha 5-containing human gamma-aminobutyric acidA receptors. Mol Pharmacol. 1993 Jun;43(6):970-5. [8391122 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA2
Uniprot ID:
P47869
Molecular Weight:
51325.85 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.103 uMNot AvailableBindingDB 26266
Inhibitory0.156 uMNot AvailableBindingDB 26266
Inhibitory0.16 uMNot AvailableBindingDB 26266
Inhibitory0.2551 uMNot AvailableBindingDB 26266
References
  1. Pritchett DB, Seeburg PH: Gamma-aminobutyric acidA receptor alpha 5-subunit creates novel type II benzodiazepine receptor pharmacology. J Neurochem. 1990 May;54(5):1802-4. [2157817 ]
  2. Smith AJ, Alder L, Silk J, Adkins C, Fletcher AE, Scales T, Kerby J, Marshall G, Wafford KA, McKernan RM, Atack JR: 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. 2001 May;59(5):1108-18. [11306694 ]
  3. Russell MG, Carling RW, Atack JR, Bromidge FA, Cook SM, Hunt P, Isted C, Lucas M, McKernan RM, Mitchinson A, Moore KW, Narquizian R, Macaulay AJ, Thomas D, Thompson SA, Wafford KA, Castro JL: Discovery of functionally selective 7,8,9,10-tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazines as GABA A receptor agonists at the alpha3 subunit. J Med Chem. 2005 Mar 10;48(5):1367-83. [15743180 ]
  4. Cox ED, Diaz-Arauzo H, Huang Q, Reddy MS, Ma C, Harris B, McKernan R, Skolnick P, Cook JM: Synthesis and evaluation of analogues of the partial agonist 6-(propyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (6-PBC) and the full agonist 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (Zk 93423) at wild type and recombinant GABAA receptors. J Med Chem. 1998 Jul 2;41(14):2537-52. [9651158 ]
  5. Huang Q, He X, Ma C, Liu R, Yu S, Dayer CA, Wenger GR, McKernan R, Cook JM: Pharmacophore/receptor models for GABA(A)/BzR subtypes (alpha1beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2) via a comprehensive ligand-mapping approach. J Med Chem. 2000 Jan 13;43(1):71-95. [10633039 ]
  6. Yin W, Majumder S, Clayton T, Petrou S, VanLinn ML, Namjoshi OA, Ma C, Cromer BA, Roth BL, Platt DM, Cook JM: Design, synthesis, and subtype selectivity of 3,6-disubstituted beta-carbolines at Bz/GABA(A)ergic receptors. SAR and studies directed toward agents for treatment of alcohol abuse. Bioorg Med Chem. 2010 Nov 1;18(21):7548-64. doi: 10.1016/j.bmc.2010.08.049. Epub 2010 Sep 29. [20888240 ]
  7. Carling RW, Moore KW, Street LJ, Wild D, Isted C, Leeson PD, Thomas S, O'Connor D, McKernan RM, Quirk K, Cook SM, Atack JR, Wafford KA, Thompson SA, Dawson GR, Ferris P, Castro JL: 3-phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-a]phthalazines and analogues: high-affinity gamma-aminobutyric acid-A benzodiazepine receptor ligands with alpha 2, alpha 3, and alpha 5-subtype binding selectivity over alpha 1. J Med Chem. 2004 Mar 25;47(7):1807-22. [15027873 ]
  8. Carling RW, Madin A, Guiblin A, Russell MG, Moore KW, Mitchinson A, Sohal B, Pike A, Cook SM, Ragan IC, McKernan RM, Quirk K, Ferris P, Marshall G, Thompson SA, Wafford KA, Dawson GR, Atack JR, Harrison T, Castro JL, Street LJ: 7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl) -1,2,4-triazolo[4,3-b]pyridazine: a functionally selective gamma-aminobutyric acid(A) (GABA(A)) alpha2/alpha3-subtype selective agonist that exhibits potent anxiolytic activity but is not sedating in animal models. J Med Chem. 2005 Nov 17;48(23):7089-92. [16279764 ]
  9. Street LJ, Sternfeld F, Jelley RA, Reeve AJ, Carling RW, Moore KW, McKernan RM, Sohal B, Cook S, Pike A, Dawson GR, Bromidge FA, Wafford KA, Seabrook GR, Thompson SA, Marshall G, Pillai GV, Castro JL, Atack JR, MacLeod AM: Synthesis and biological evaluation of 3-heterocyclyl-7,8,9,10-tetrahydro-(7,10-ethano)-1,2,4-triazolo[3,4-a]phthalazine s and analogues as subtype-selective inverse agonists for the GABA(A)alpha5 benzodiazepine binding site. J Med Chem. 2004 Jul 1;47(14):3642-57. [15214791 ]
General Function:
Gaba-gated chloride ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
Gene Name:
GABRB3
Uniprot ID:
P28472
Molecular Weight:
54115.04 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0267 uMNot AvailableBindingDB 26266
Inhibitory0.027 uMNot AvailableBindingDB 26266
Inhibitory0.0521 uMNot AvailableBindingDB 26266
Inhibitory0.383 uMNot AvailableBindingDB 26266
Inhibitory>10 uMNot AvailableBindingDB 26266
Inhibitory>15 uMNot AvailableBindingDB 26266
Inhibitory>3.333 uMNot AvailableBindingDB 26266
References
  1. Cox ED, Diaz-Arauzo H, Huang Q, Reddy MS, Ma C, Harris B, McKernan R, Skolnick P, Cook JM: Synthesis and evaluation of analogues of the partial agonist 6-(propyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (6-PBC) and the full agonist 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (Zk 93423) at wild type and recombinant GABAA receptors. J Med Chem. 1998 Jul 2;41(14):2537-52. [9651158 ]
  2. Yin W, Majumder S, Clayton T, Petrou S, VanLinn ML, Namjoshi OA, Ma C, Cromer BA, Roth BL, Platt DM, Cook JM: Design, synthesis, and subtype selectivity of 3,6-disubstituted beta-carbolines at Bz/GABA(A)ergic receptors. SAR and studies directed toward agents for treatment of alcohol abuse. Bioorg Med Chem. 2010 Nov 1;18(21):7548-64. doi: 10.1016/j.bmc.2010.08.049. Epub 2010 Sep 29. [20888240 ]
  3. Huang Q, He X, Ma C, Liu R, Yu S, Dayer CA, Wenger GR, McKernan R, Cook JM: Pharmacophore/receptor models for GABA(A)/BzR subtypes (alpha1beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2) via a comprehensive ligand-mapping approach. J Med Chem. 2000 Jan 13;43(1):71-95. [10633039 ]
  4. Carling RW, Moore KW, Street LJ, Wild D, Isted C, Leeson PD, Thomas S, O'Connor D, McKernan RM, Quirk K, Cook SM, Atack JR, Wafford KA, Thompson SA, Dawson GR, Ferris P, Castro JL: 3-phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-a]phthalazines and analogues: high-affinity gamma-aminobutyric acid-A benzodiazepine receptor ligands with alpha 2, alpha 3, and alpha 5-subtype binding selectivity over alpha 1. J Med Chem. 2004 Mar 25;47(7):1807-22. [15027873 ]
  5. Russell MG, Carling RW, Atack JR, Bromidge FA, Cook SM, Hunt P, Isted C, Lucas M, McKernan RM, Mitchinson A, Moore KW, Narquizian R, Macaulay AJ, Thomas D, Thompson SA, Wafford KA, Castro JL: Discovery of functionally selective 7,8,9,10-tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazines as GABA A receptor agonists at the alpha3 subunit. J Med Chem. 2005 Mar 10;48(5):1367-83. [15743180 ]
  6. Carling RW, Madin A, Guiblin A, Russell MG, Moore KW, Mitchinson A, Sohal B, Pike A, Cook SM, Ragan IC, McKernan RM, Quirk K, Ferris P, Marshall G, Thompson SA, Wafford KA, Dawson GR, Atack JR, Harrison T, Castro JL, Street LJ: 7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl) -1,2,4-triazolo[4,3-b]pyridazine: a functionally selective gamma-aminobutyric acid(A) (GABA(A)) alpha2/alpha3-subtype selective agonist that exhibits potent anxiolytic activity but is not sedating in animal models. J Med Chem. 2005 Nov 17;48(23):7089-92. [16279764 ]
  7. Street LJ, Sternfeld F, Jelley RA, Reeve AJ, Carling RW, Moore KW, McKernan RM, Sohal B, Cook S, Pike A, Dawson GR, Bromidge FA, Wafford KA, Seabrook GR, Thompson SA, Marshall G, Pillai GV, Castro JL, Atack JR, MacLeod AM: Synthesis and biological evaluation of 3-heterocyclyl-7,8,9,10-tetrahydro-(7,10-ethano)-1,2,4-triazolo[3,4-a]phthalazine s and analogues as subtype-selective inverse agonists for the GABA(A)alpha5 benzodiazepine binding site. J Med Chem. 2004 Jul 1;47(14):3642-57. [15214791 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular Weight:
51801.395 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0207 uMNot AvailableBindingDB 26266
Inhibitory0.041 uMNot AvailableBindingDB 26266
Inhibitory0.1119 uMNot AvailableBindingDB 26266
IC500.014 uMNot AvailableBindingDB 26266
IC500.13 uMNot AvailableBindingDB 26266
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
  4. Hadingham KL, Garrett EM, Wafford KA, Bain C, Heavens RP, Sirinathsinghji DJ, Whiting PJ: Cloning of cDNAs encoding the human gamma-aminobutyric acid type A receptor alpha 6 subunit and characterization of the pharmacology of alpha 6-containing receptors. Mol Pharmacol. 1996 Feb;49(2):253-9. [8632757 ]
  5. Scholze P, Ebert V, Sieghart W: Affinity of various ligands for GABAA receptors containing alpha 4 beta 3 gamma 2, alpha 4 gamma 2, or alpha 1 beta 3 gamma 2 subunits. Eur J Pharmacol. 1996 May 23;304(1-3):155-62. [8813598 ]
  6. Hadingham KL, Wingrove P, Le Bourdelles B, Palmer KJ, Ragan CI, Whiting PJ: Cloning of cDNA sequences encoding human alpha 2 and alpha 3 gamma-aminobutyric acidA receptor subunits and characterization of the benzodiazepine pharmacology of recombinant alpha 1-, alpha 2-, alpha 3-, and alpha 5-containing human gamma-aminobutyric acidA receptors. Mol Pharmacol. 1993 Jun;43(6):970-5. [8391122 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA6
Uniprot ID:
Q16445
Molecular Weight:
51023.69 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 26266
Inhibitory>15 uMNot AvailableBindingDB 26266
References
  1. Hadingham KL, Garrett EM, Wafford KA, Bain C, Heavens RP, Sirinathsinghji DJ, Whiting PJ: Cloning of cDNAs encoding the human gamma-aminobutyric acid type A receptor alpha 6 subunit and characterization of the pharmacology of alpha 6-containing receptors. Mol Pharmacol. 1996 Feb;49(2):253-9. [8632757 ]
  2. Hanson SM, Morlock EV, Satyshur KA, Czajkowski C: Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem. 2008 Nov 27;51(22):7243-52. doi: 10.1021/jm800889m. [18973287 ]
General Function:
Cholesterol binding
Specific Function:
Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678).
Gene Name:
TSPO
Uniprot ID:
P30536
Molecular Weight:
18827.81 Da
References
  1. Berson A, Descatoire V, Sutton A, Fau D, Maulny B, Vadrot N, Feldmann G, Berthon B, Tordjmann T, Pessayre D: Toxicity of alpidem, a peripheral benzodiazepine receptor ligand, but not zolpidem, in rat hepatocytes: role of mitochondrial permeability transition and metabolic activation. J Pharmacol Exp Ther. 2001 Nov;299(2):793-800. [11602696 ]
  2. Trapani G, Franco M, Ricciardi L, Latrofa A, Genchi G, Sanna E, Tuveri F, Cagetti E, Biggio G, Liso G: Synthesis and binding affinity of 2-phenylimidazo[1,2-alpha]pyridine derivatives for both central and peripheral benzodiazepine receptors. A new series of high-affinity and selective ligands for the peripheral type. J Med Chem. 1997 Sep 12;40(19):3109-18. [9301675 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA4
Uniprot ID:
P48169
Molecular Weight:
61622.645 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 26266
References
  1. Scholze P, Ebert V, Sieghart W: Affinity of various ligands for GABAA receptors containing alpha 4 beta 3 gamma 2, alpha 4 gamma 2, or alpha 1 beta 3 gamma 2 subunits. Eur J Pharmacol. 1996 May 23;304(1-3):155-62. [8813598 ]