Zolpidem

Basic Info

Common NameZolpidem(F04752)
2D Structure
Description

Zolpidem (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.

FRCD IDF04752
CAS Number82626-48-0
PubChem CID5732
FormulaC19H21N3O
IUPAC Name

N,N-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide

InChI Key

ZAFYATHCZYHLPB-UHFFFAOYSA-N

InChI

InChI=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

Canonical SMILES

CC1=CC=C(C=C1)C2=C(N3C=C(C=CC3=N2)C)CC(=O)N(C)C

Isomeric SMILES

CC1=CC=C(C=C1)C2=C(N3C=C(C=CC3=N2)C)CC(=O)N(C)C

WikipediaZolpidem
Synonyms
        
            N,N-Dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide
        
            zolpidem
        
            82626-48-0
        
            Ambien
        
            Zolpidemum
        
            Lorex
        
            Zolpidemum [Latin]
        
            Zolpidem [INN:BAN]
        
            [3H]zolpidem
        
            UNII-7K383OQI23
Classifies
                

                  
                    Illegal Additives
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassOrganoheterocyclic compounds
ClassAzoles
SubclassImidazoles
Intermediate Tree NodesSubstituted imidazoles
Direct ParentPhenylimidazoles
Alternative Parents
Molecular FrameworkAromatic heteropolycyclic compounds
Substituents5-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
DescriptionThis compound 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.

Properties

Property NameProperty Value
Molecular Weight307.397
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count2
Rotatable Bond Count3
Complexity417
Monoisotopic Mass307.168
Exact Mass307.168
XLogP2.5
Formal Charge0
Heavy Atom Count23
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.9392
Human Intestinal AbsorptionHIA+1.0000
Caco-2 PermeabilityCaco2+0.6638
P-glycoprotein SubstrateSubstrate0.5000
P-glycoprotein InhibitorInhibitor0.8564
Non-inhibitor0.7574
Renal Organic Cation TransporterNon-inhibitor0.6210
Distribution
Subcellular localizationMitochondria0.8441
Metabolism
CYP450 2C9 SubstrateNon-substrate0.7412
CYP450 2D6 SubstrateSubstrate0.8918
CYP450 3A4 SubstrateSubstrate0.7407
CYP450 1A2 InhibitorInhibitor0.6240
CYP450 2C9 InhibitorNon-inhibitor0.8331
CYP450 2D6 InhibitorNon-inhibitor0.8754
CYP450 2C19 InhibitorNon-inhibitor0.9119
CYP450 3A4 InhibitorNon-inhibitor0.8309
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.5265
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9831
Non-inhibitor0.6928
AMES ToxicityNon AMES toxic0.5507
CarcinogensNon-carcinogens0.8352
Fish ToxicityHigh FHMT0.7269
Tetrahymena Pyriformis ToxicityHigh TPT0.6619
Honey Bee ToxicityLow HBT0.8366
BiodegradationNot ready biodegradable0.9928
Acute Oral ToxicityIII0.8022
Carcinogenicity (Three-class)Non-required0.6465
Model Value Unit
Absorption
Aqueous solubility-2.5852LogS
Caco-2 Permeability1.3981LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.5614LD50, mol/kg
Fish Toxicity1.1439pLC50, mg/L
Tetrahymena Pyriformis Toxicity0.5693pIGC50, ug/L

Targets

Target Details

Gamma-aminobutyric acid receptor subunit alpha-2

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
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 ]
Target Details

Gamma-aminobutyric acid receptor subunit beta-3

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
References
  1. 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 ]
Target Details

Gamma-aminobutyric acid receptor subunit alpha-6

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
References
  1. 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 ]
Target Details

Translocator protein

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
Mechanism of Action:
Zolpidem modulates the alpha-subunit, known as the benzodiazepine receptor, within the GABA<sub>A</sub> 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.
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 ]
Target Details

Gamma-aminobutyric acid receptor subunit alpha-4

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
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 ]
Target Details

Gamma-aminobutyric acid receptor subunit alpha-3

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
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 ]
Target Details

Gamma-aminobutyric acid receptor subunit alpha-1

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
Mechanism of Action:
Zolpidem modulates the alpha-subunit, known as the benzodiazepine receptor, within the GABA<sub>A</sub> 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.
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 ]