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Showing drug card for Zolpidem (DB00425)

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Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:05:57
Primary Accession Number DB00425
Secondary Accession Number
  • APRD00095
Name Zolpidem
Drug Type
  • Approved
  • Small Molecule
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]
Synonyms
  1. Zolpidem tartrate
  2. Zolpidemum [Latin]
Brand Names
  1. Ambien
  2. Ivadal
  3. Lorex
  4. Niotal
  5. Stilnoct
  6. Stilnox
Brand Mixtures Not Available
Chemical IUPAC Name N,N-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[3,2-a]pyridin-3-yl]acetamide
Chemical Formula C19H21N3O
Chemical Structure Structure
CAS Registry Number 82626-48-0
InChI Identifier InChI=1/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 Key ZAFYATHCZYHLPB-UHFFFAOYAM
KEGG Drug Not Available
KEGG Compound C07219 Link Image
PubChem Compound 5732 Link Image
PubChem Substance 199579 Link Image
ChEBI ID Not Available
PharmGKB ID PA451976 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] Not Available
RxList Link http://www.rxlist.com/cgi/generic/zolpid.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Zolpidem Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference J. P. Kaplan, P. George., U.S. Pat. 4,382,938 (1983)
Average Molecular Weight 307.3895
Monoisotopic Molecular Weight 307.1685
State Solid
Melting Point 196 oC
Experimental Water Solubility 23 mg/mL Source: PhysProp
Predicted Water Solubility 3.13e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 1.2 Source: PhysProp
Predicted LogP 3.15 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -3.99 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 6.2
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CN(C)C(=O)CC1=C(N=C2C=CC(C)=CN12)C1=CC=C(C)C=C1
Canonical SMILES CN(C)C(=O)CC1=C(N=C2C=CC(C)=CN12)C1=CC=C(C)C=C1
Drug Category
  • GABA Agonists
  • Hypnotics and Sedatives
ATC Codes
AHFS Codes Not Available
Indication For the short-term treatment of insomnia.
Pharmacology 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.
Toxicity Oral (male rat) LD50 = 695 mg/kg. Symptoms of overdose include impairment of consciousness ranging from somnolence to light coma.
Protein Binding 92.5 ± 0.1% (independent of concentration between 40 and 790 ng/mL)
Biotransformation Zolpidem is converted to inactive metabolites in the liver.
Half Life 2.6 hours
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Take 30-60 minutes before breakfast.
Pathways Not Available
General References
  1. 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 Link Image]
  2. 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 Link Image]
  3. 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 Link Image]
  4. Lemmer B: The sleep-wake cycle and sleeping pills. Physiol Behav. 2007 Feb 28;90(2-3):285-93. Epub 2006 Oct 16. [PubMed Link Image]
  5. 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 Link Image]
  6. Drugs.com Link Image
  7. Wikipedia Link Image
  8. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A4 (CYP3A4)
Targets
  1. Translocator protein
  2. Gamma-aminobutyric-acid receptor subunit alpha-1
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 1 Gene Name CYP3A4
Enzyme 1 SwissProt ID P08684 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Drug Target 1 [top]
Target 1 ID 811
Target 1 Name Translocator protein
Target 1 Synonyms
  1. Mitochondrial benzodiazepine receptor
  2. PBR
  3. PKBS
  4. Peripheral-type benzodiazepine receptor
Target 1 Gene Name BZRP
Target 1 Protein Sequence >Peripheral-type benzodiazepine receptor 
MAPPWVPAMGFTLAPSLGCFVGSRFVHGEGLRWYAGLQKPSWHPPHWVLGPVWGTLYSAM
GYGSYLVWKELGGFTEKAVVPLGLYTGQLALNWAWPPIFFGARQMGWALVDLLLVSGAAA
ATTVAWYQVSPLAARLLYPYLAWLAFATTLNYCVWRDNHGWHGGRRLPE
Target 1 Number of Residues 171
Target 1 Molecular Weight 18779
Target 1 Theoretical pI 9.33
Target 1 GO Classification
Function
Not Available
Process
Not Available
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Signal transduction mechanisms
Target 1 Specific Function Responsible for the manifestation of peripheral-type benzodiazepine recognition sites and is most likely to comprise binding domains for benzodiazepines and isoquinoline carboxamides. May play a role in the transport of porphyrins and heme
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 6-26
  • 47-67
  • 80-100
  • 106-126
  • 135-155
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 306883 Link Image
Target 1 UniProtKB/Swiss-Prot ID P30536 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name BZRP_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Mitochondrion
  • mitochondrial membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >510 bp 
ATGGCCCCGCCCTGGGTGCCCGCCATGGGCTTCACGCTGGCGCCCAGCCTGGGGTGCTTC
GTGGGCTCCCGCTTTGTCCACGGCGAGGGTCTCCGCTGGTACGCCGGCCTGCAGAAGCCC
TCGTGGCACCCGCCCCACTGGGTGCTGGGCCCTGTCTGGGGCACGCTCTACTCAGCCATG
GGGTACGGCTCCTACCTGGTCTGGAAAGAGCTGGGAGGCTTCACAGAGAAGGCTGTGGTT
CCCCTGGGCCTCTACACTGGGCAGCTGGCCCTGAACTGGGCATGGCCCCCCATCTTCTTT
GGTGCCCGACAAATGGGCTGGGCCTTGGTGGATCTCCTGCTGGTCAGTGGGGCGGCGGCN
GCCACTACCGTGGCCTGGTACCAGGTGAGCCCGCTGGCCGCCCGCCTGCTCTACCCCTAC
CTGGCCTGGCTGGCCTTCGCGACCACACTCAACTACTGCGTATGGCGGGACAACCATGGC
TGGCATGGGGGACGGCGGCTGCCAGAGTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID TSPO Link Image
Target 1 GenAtlas ID TSPO Link Image
Target 1 HGNC ID HGNC:1158 Link Image
Target 1 Chromosome Location 22
Target 1 Locus 22q13.31
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. [PubMed Link Image]
  2. Kurumaji A, Nomoto H, Yoshikawa T, Okubo Y, Toru M: An association study between two missense variations of the benzodiazepine receptor (peripheral) gene and schizophrenia in a Japanese sample. J Neural Transm. 2000;107(4):491-500. [PubMed Link Image]
  3. Kurumaji A, Nomoto H, Yamada K, Yoshikawa T, Toru M: No association of two missense variations of the benzodiazepine receptor (peripheral) gene and mood disorders in a Japanese sample. Am J Med Genet. 2001 Mar 8;105(2):172-5. [PubMed Link Image]
  4. Riond J, Mattei MG, Kaghad M, Dumont X, Guillemot JC, Le Fur G, Caput D, Ferrara P: Molecular cloning and chromosomal localization of a human peripheral-type benzodiazepine receptor. Eur J Biochem. 1991 Jan 30;195(2):305-11. [PubMed Link Image]
  5. Yakovlev AG, Ruffo M, Jurka J, Krueger KE: Comparison of repetitive elements in the third intron of human and rodent mitochondrial benzodiazepine receptor-encoding genes. Gene. 1995 Apr 3;155(2):201-5. [PubMed Link Image]
  6. Galiegue S, Jbilo O, Combes T, Bribes E, Carayon P, Le Fur G, Casellas P: Cloning and characterization of PRAX-1. A new protein that specifically interacts with the peripheral benzodiazepine receptor. J Biol Chem. 1999 Jan 29;274(5):2938-52. [PubMed Link Image]
Target 1 Drug 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. [PubMed Link Image]
  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. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 872
Target 2 Name Gamma-aminobutyric-acid receptor subunit alpha-1
Target 2 Synonyms
  1. Gamma-aminobutyric-acid receptor subunit alpha-1 precursor
Target 2 Gene Name GABRA1
Target 2 Protein Sequence >Gamma-aminobutyric-acid receptor subunit alpha-1 precursor 
MRKSPGLSDCLWAWILLLSTLTGRSYGQPSLQDELKDNTTVFTRILDRLLDGYDNRLRPG
LGERVTEVKTDIFVTSFGPVSDHDMEYTIDVFFRQSWKDERLKFKGPMTVLRLNNLMASK
IWTPDTFFHNGKKSVAHNMTMPNKLLRITEDGTLLYTMRLTVRAECPMHLEDFPMDAHAC
PLKFGSYAYTRAEVVYEWTREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVM
TTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISA
RNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRGYAWDGKSVVPEKPKKVKDP
LIKKNNTYAPTATSYTPNLARGDPGLATIAKSATIEPKEVKPETKPPEPKKTFNSVSKID
RLSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ
Target 2 Number of Residues 463
Target 2 Molecular Weight 51802
Target 2 Theoretical pI 9.61
Target 2 GO Classification
Function
neurotransmitter receptor activity
transporter activity
ion transporter activity
ion channel activity
ligand-gated ion channel activity
extracellular ligand-gated ion channel activity
signal transducer activity
receptor activity
transmembrane receptor activity
GABA receptor activity
GABA-A receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
gamma-aminobutyric acid signaling pathway
anion transport
inorganic anion transport
chloride transport
physiological process
cellular physiological process
transport
ion transport
Component
postsynaptic membrane
cell
membrane
intrinsic to membrane
integral to membrane
Target 2 General Function Involved in GABA-A receptor activity
Target 2 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
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-27
Target 2 Transmembrane Regions
  • 252-273
  • 279-300
  • 313-334
  • 422-443
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 31631 Link Image
Target 2 UniProtKB/Swiss-Prot ID P14867 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name GBRA1_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 2 Gene Sequence >1371 bp 
ATGAGGAAAAGTCCAGGTCTGTCTGACTGTCTTTGGGCCTGGATCCTCCTTCTGAGCACA
CTGACTGGAAGAAGCTATGGACAGCCGTCATTACAAGATGAACTTAAAGACAATACCACT
GTCTTCACCAGGATTTTGGACAGACTCCTAGATGGTTATGACAATCGCCTGAGACCAGGA
TTGGGAGAGCGTGTAACCGAAGTGAAGACTGATATCTTCGTCACCAGTTTCGGACCCGTT
TCAGACCATGATATGGAATATACAATAGATGTATTTTTCCGTCAAAGCTGGAAGGATGAA
AGGTTAAAATTTAAAGGACCTATGACAGTCCTCCGGTTAAATAACCTAATGGCAAGTAAA
ATCTGGACTCCGGACACATTTTTCCACAATGGAAAGAAGTCAGTGGCCCACAACATGACC
ATGCCCAACAAACTCCTGCGGATCACAGAGGATGGCACCTTGCTGTACACCATGAGGCTG
ACAGTGAGAGCTGAATGTCCGATGCATTTGGAGGACTTCCCTATGGATGCCCATGCTTGC
CCACTAAAATTTGGAAGTTATGCTTATACAAGAGCAGAAGTTGTTTATGAATGGACCAGA
GAGCCAGCACGCTCAGTGGTTGTAGCAGAAGATGGATCACGTCTAAACCAGTATGACCTT
CTTGGACAAACAGTAGACTCTGGAATTGTCCAGTCAAGTACAGGAGAATATGTTGTTATG
ACCACTCATTTCCACTTGAAGAGAAAGATTGGCTACTTTGTTATTCAAACATACCTGCCA
TGCATAATGACAGTGATTCTCTCACAAGTCTCCTTCTGGCTCAACAGAGAGTCTGTACCA
GCAAGAACTGTCTTTGGAGTAACAACTGTGCTCACCATGACAACATTGAGCATCAGTGCC
AGAAACTCCCTCCCTAAGGTGGCTTATGCAACAGCTATGGATTGGTTTATTGCCGTGTGC
TATGCCTTTGTGTTCTCAGCTCTGATTGAGTTTGCCACAGTAAACTATTTCACTAAGAGA
GGTTATGCATGGGATGGCAAAAGTGTGGTTCCAGAAAAGCCAAAGAAAGTAAAGGATCCT
CTTATTAAGAAAAACAACACTTACGCTCCAACAGCAACCAGCTACACCCCTAATTTGGCC
AGGGGCGACCCGGGCTTAGCCACCATTGCTAAAAGTGCAACCATAGAACCTAAAGAGGTC
AAGCCCGAAACAAAACCACCAGAACCCAAGAAAACCTTTAACAGTGTCAGCAAAATTGAC
CGACTGTCAAGAATAGCCTTCCCGCTGCTATTTGGAATCTTTAACTTAGTCTACTGGGCT
ACGTATTTAAACAGAGAGCCTCAGCTAAAAGCCCCCACACCACATCAATAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID GABRA1 Link Image
Target 2 GenAtlas ID GABRA1 Link Image
Target 2 HGNC ID HGNC:4075 Link Image
Target 2 Chromosome Location 5
Target 2 Locus 5q34-q35
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Cossette P, Liu L, Brisebois K, Dong H, Lortie A, Vanasse M, Saint-Hilaire JM, Carmant L, Verner A, Lu WY, Wang YT, Rouleau GA: Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nat Genet. 2002 Jun;31(2):184-9. Epub 2002 May 6. [PubMed Link Image]
  2. Schofield PR, Pritchett DB, Sontheimer H, Kettenmann H, Seeburg PH: Sequence and expression of human GABAA receptor alpha 1 and beta 1 subunits. FEBS Lett. 1989 Feb 27;244(2):361-4. [PubMed Link Image]
  3. Garrett KM, Duman RS, Saito N, Blume AJ, Vitek MP, Tallman JF: Isolation of a cDNA clone for the alpha subunit of the human GABA-A receptor. Biochem Biophys Res Commun. 1988 Oct 31;156(2):1039-45. [PubMed Link Image]
Target 2 Drug References
  1. 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 Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

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