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targets (3) enzymes (8)
for drugs
Identification
Name Zolpidem
Accession Number DB00425 (APRD00095)
Type small molecule
Groups approved
Description

Zolpidem is a prescription short-acting nonbenzodiazepine hypnotic that potentiates gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, by binding to benzodiazepine receptors which are located on the gamma-aminobutyric acid receptors. Zolpidem is used for the short-term treatment of insomnia. It works quickly (usually within 15 minutes) and has a short half-life (2-3 hours). It is classified as an imidazopyridine. As an anticonvulsant and muscle relaxant, the beneficial effects start to emerge at 10 and 20 times the dose required for sedation, respectively. For that reason, it has never been approved for either muscle relaxation or seizure prevention. Recently, zolpidem has been cited in various medical reports mainly in the United Kingdom as waking persistent vegetative state (PVS) patients, and dramatically improving the conditions of people with brain injuries. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Zolpidem tartrate
  • Zolpidemum [Latin]
Brand names
  • Ambien
  • Ambien CR
  • Ivadal
  • Lorex
  • Niotal
  • Stilnoct
  • Stilnox
Brand name mixtures Not Available
Categories
  • GABA Agonists
  • Hypnotics and Sedatives
CAS number 82626-48-0
Weight Average: 307.3895
Monoisotopic: 307.168462309
Chemical Formula C19H21N3O
InChI Key InChIKey=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
Plain Text
IUPAC Name
N,N-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide
SMILES
CN(C)C(=O)CC1=C(N=C2C=CC(C)=CN12)C1=CC=C(C)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylpropenes
  • Imidazopyridines
Substructures
  • Amino Ketones
  • Phenylpropenes
  • Pyridines and Derivatives
  • Imidazopyridines
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Imines
  • Cyanamides
Pharmacology
Indication For the short-term treatment of insomnia.
Pharmacodynamics Zolpidem is a sedative or hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties. It interacts with a GABA-BZ receptor complex and shares some of the pharmacological properties of the benzodiazepines. In contrast to the benzodiazepines, which non-selectively bind to and activate all three alpha receptor subtypes, zolpidem in vitro binds the (alpha1) receptor preferentially. The (alpha1) receptor is found primarily on the Lamina IV of the sensorimotor cortical regions, substantia nigra (pars reticulata), cerebellum molecular layer, olfactory bulb, ventral thalamic complex, pons, inferior colliculus, and globus pallidus.
Mechanism of action Zolpidem 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.
Absorption Zolpidem is rapidly absorbed from the GI tract.
Volume of distribution Not Available
Protein binding 92.5 ± 0.1% (independent of concentration between 40 and 790 ng/mL)
Metabolism

Zolpidem is converted to inactive metabolites in the liver.

Enzyme Metabolite Reaction Km Vmax
Prostaglandin G/H synthase 1 methoxylation
Cytochrome P450 2D6 methoxylation
Cytochrome P450 2D6 methoxylation
Cytochrome P450 1A2 methoxylation
Cytochrome P450 1A2 methoxylation
Cytochrome P450 3A4 methoxylation
Cytochrome P450 3A4 methoxylation
Cytochrome P450 2C9 methoxylation
Cytochrome P450 2C19 methoxylation
Route of elimination Zolpidem tartrate tablets are converted to inactive metabolites that are eliminated primarily by renal excretion.
Half life 2.6 hours
Clearance Not Available
Toxicity Oral (male rat) LD50 = 695 mg/kg. Symptoms of overdose include impairment of consciousness ranging from somnolence to light coma.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Novadel pharma inc
  • Sanofi aventis us llc
  • Biovail laboratories international srl
  • Apotex inc
  • Aurobindo pharma ltd
  • Caraco pharmaceutical laboratories ltd
  • Carlsbad technology inc
  • Dr reddys laboratories ltd
  • Genpharm inc
  • Hikma pharmaceuticals
  • Invagen pharmaceuticals inc
  • Lek pharmaceuticals dd
  • Mutual pharmacal co
  • Mylan pharmaceuticals inc
  • Ranbaxy laboratories ltd
  • Roxane laboratories inc
  • Synthon pharmaceuticals ltd
  • Teva pharmaceuticals usa inc
  • Torrent pharmaceuticals ltd
  • Vintage pharmaceuticals llc
  • Watson laboratories inc
  • Wockhardt ltd
  • World gen llc
  • Meda pharmaceuticals
  • Pfizer Inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Ambien cr 12.5 mg tablet 6.19 USD tablet
Ambien cr 6.25 mg tablet 6.19 USD tablet
Ambien 10 mg tablet 6.11 USD tablet
Ambien 5 mg tablet 6.04 USD tablet
Ambien CR 12.5 mg Controlled Release Tabs 6.0 USD tab
Ambien CR 6.25 mg Controlled Release Tabs 6.0 USD tab
Edluar 10 mg sl tablet 5.0 USD tablet
Edluar 5 mg sl tablet 5.0 USD tablet
Zolpidem tartrate 10 mg tablet 2.73 USD tablet
Zolpidem tartrate 5 mg tablet 2.73 USD tablet
Patents
Country Patent Number Approved Expires
United States 6514531 2000-06-01 2020-06-01
United States 7632517 1997-10-01 2017-10-01
Properties
State solid
Melting point 196 oC
Experimental Properties
Property Value Source
water solubility 23 mg/mL PhysProp
logP 1.2 PhysProp
pKa 6.2 Various sources
Predicted Properties
Property Value Source
water solubility 3.13e-02 g/l ALOGPS
logP 3.15 ALOGPS
logP 3.02 ChemAxon Molconvert
logS -3.99 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 37.61 ChemAxon Molconvert
rotatable bond count 3 ChemAxon Molconvert
refractivity 93.58 ChemAxon Molconvert
polarizability 35.06 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Lemmer B: The sleep-wake cycle and sleeping pills. Physiol Behav. 2007 Feb 28;90(2-3):285-93. Epub 2006 Oct 16. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
External Links
Resource Link
KEGG Compound C07219 Link_out
PubChem Compound 5732 Link_out
PubChem Substance 46507949 Link_out
ChemSpider 5530 Link_out
BindingDB 26266 Link_out
ChEBI 10125 Link_out
ChEMBL 10125 Link_out
Therapeutic Targets Database DAP000112 Link_out
PharmGKB PA451976 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic/zolpid.htm Link_out
Drugs.com http://www.drugs.com/zolpidem.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Zolpidem Link_out
ATC Codes
  • N05CF02
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (322.6 KB)
MSDS show (170.1 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Should not be administered with or immediately after a meal.
Targets

1. Gamma-aminobutyric-acid receptor subunit alpha-1

Pharmacological action: yes
Actions: potentiator

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

Organism class: human
UniProt ID: P14867 Link_out
Gene: GABRA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
  3. Vlainic J, Pericic D: Effects of acute and repeated zolpidem treatment on pentylenetetrazole-induced seizure threshold and on locomotor activity: comparison with diazepam. Neuropharmacology. 2009 Jun;56(8):1124-30. Epub 2009 Apr 1. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed

2. Gamma-aminobutyric-acid receptor subunit alpha-2

Pharmacological action: unknown
Actions: agonist

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

Organism class: human
UniProt ID: P47869 Link_out
Gene: GABRA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed

3. Gamma-aminobutyric-acid receptor subunit alpha-3

Pharmacological action: unknown
Actions: agonist

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

Organism class: human
UniProt ID: P34903 Link_out
Gene: GABRA3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
Enzymes

1. Cytochrome P450 3A5

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

2. Cytochrome P450 3A7

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

3. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

4. Cytochrome P450 1A2

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. Pubmed
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

5. Cytochrome P450 2C9

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

6. Cytochrome P450 2C19

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

7. Cytochrome P450 2D6

Actions: substrate

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

8. Prostaglandin G/H synthase 1

Actions: substrate

May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells

UniProt ID: P23219 Link_out
Gene: PTGS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:03

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.