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

• ChemBase ID: 308
• Molecular Formular: C19H21N3O
• Molecular Mass: 307.38954
• Monoisotopic Mass: 307.16846231
• SMILES: O=C(N(C)C)Cc1n2c(nc1c1ccc(cc1)C)ccc(c2)C
• Canonical SMILES: Cc1ccc(cc1)c1nc2n(c1CC(=O)N(C)C)cc(cc2)C
• 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
• InChIKey: ZAFYATHCZYHLPB-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N,N-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide
• IUPAC Traditional name: zolpidem
• Brand Name: Ambien; Ivadal; Lorex; Niotal; Stilnoct; Stilnox; Ambien CR
• Synonyms: Zolpidemum [Latin]; Zolpidem tartrate; Zolpidem; N,N,6-Trimethyl-2-(4-methylphenyl)-imidazo[1,2-a]pyridine-3-acetamide; Zolpidem; N,N,6-Trimethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3-acetamide; N,N,6-Trimethyl-2-p-tolylimidazol[1,2-a]pyridine-3-acetamide; SL 80-0750; SL 800750; ZOLPIDEM TARTRATE

Database IDs

• CAS Number: 99294-93-6; 82626-48-0
• MDL Number: MFCD00153885
• PubChem SID: 24902172; 46507949; 160963771
• PubChem CID: 5732
• CHEBI ID: 10125
• ATC CODE: N05CF02
• CHEMBL: 911
• Chemspider ID: 5530
• DrugBank ID: DB00425
• KEGG ID: D08690
• Unique Ingredient Identifier: 7K383OQI23
• Wikipedia Title: Zolpidem
• Medline Plus: a693025

CALCULATED PROPERTIES

JChem

• H Acceptors: 2
• H Donor: 0
• LogD (pH = 5.5): 2.6505303
• LogD (pH = 7.4): 3.0101333
• Log P: 3.0176268
• Molar Refractivity: 93.5837 cm^3
• Polarizability: 36.373756 Å^3
• Polar Surface Area: 37.61 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.15
• LOG S: -3.99
• Solubility (Water): 3.13e-02 g/l

PROPERTIES

Physical Property

• Solubility: 23 mg/mL; 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: soluble0.3 mg/mL; Chloroform; dilute aqueous base: insoluble; DMSO: >10 mg/mL; ethanol: soluble50 mg/mL; H2O: insoluble; methanol: soluble50 mg/mL
• Apperance: Off-White Solid; white solid
• Melting Point: 189-191°C
• Hydrophobicity(logP): 1.2

Safety Information

• Storage Condition: Controlled Substance, -20°C Freezer
• RTECS: NJ5109750
• German water hazard class: 3
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• Drug Control: USDEA Schedule IV; Home Office Schedule 4.1; psychotrope; kontrollierte Droge in Deutschland; regulated under CDSA - not available from Sigma-Aldrich Canada

Pharmacology Properties

• Admin Routes: Oral (tablet), Sublingual, Oromucosal (spray)
• Bioavailability: 70% (oral) 92% bound in plasma
• Excretion: 56% renal; 34% fecal
• Half Life: 2 to 3 hours
• Metabolism: Hepatic – CYP3A4
• Legal Status: CD (UK); Schedule IV (US)
• Pregnancy Category: B3 (Australia); C (US)
• Gene Information: human ... GABRA1(2554), GABRA2(2555), GABRA3(2556), GABRA5(2558), GABRA6(2559)rat ... Gabra1(29705), Gabra2(29706), Gabra5(29707), Tspo(24230)

Product Information

• Purity: ≥98% (HPLC); 98%
• Empirical Formula (Hill Notation): C19H21N3O

DETAILS

DrugBank - DB00425

• Drug 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]
• 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.
• 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
• Biotransformation: Zolpidem is converted to inactive metabolites in the liver.
• Absorption: Zolpidem is rapidly absorbed from the GI tract.
• Half Life: 2.6 hours
• Protein Binding: 92.5 ± 0.1% (independent of concentration between 40 and 790 ng/mL)
• Elimination: Zolpidem tartrate tablets are converted to inactive metabolites that are eliminated primarily by renal excretion.
• References: Lemmer B: The sleep-wake cycle and sleeping pills. Physiol Behav. 2007 Feb 28;90(2-3):285-93. Epub 2006 Oct 16. [Pubmed] ; 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] ; 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] ; 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] ; 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: Wikipedia; RxList; Drugs.com

Sigma Aldrich - Z103

Biochem/physiol Actions
Potent and selective agonist for the benzodiazepine receptor associated with the GABAA receptor; hypnotic.

Toronto Research Chemicals - Z650000

A selective non-benzodiazepine GABAA receptor agonist. Sedative, hypnotic. Controlled substance (depresssant).

REFERENCES

• 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
• 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
• Lemmer B: The sleep-wake cycle and sleeping pills. Physiol Behav. 2007 Feb 28;90(2-3):285-93. Epub 2006 Oct 16. Pubmed
• 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
• 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
• Arbilla, S., et al.: Arch. Pharmacol., 330, 248 (1985)
• Cashman, J.N., et al.: Brit. J. Clin. Pharmacol., 21, 205 (1986)