Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C19H21N3O.ClH |
| Molecular Weight | 343.85 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CN(C)C(=O)CC1=C(N=C2C=CC(C)=CN12)C3=CC=C(C)C=C3
InChI
InChIKey=TUNYMMOIJWPUHG-UHFFFAOYSA-N
InChI=1S/C19H21N3O.ClH/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;1H
Zolpidem is usually used for the treatment of insomnia as a hypnotic drug. It was also suggested to be effective in the treatment of dystonia in some studies. Zolpidem can be one of useful alternative pharmacological treatments for blepharospasm. Zolpidem 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 BZ receptor subtypes, zolpidem in vitro binds the BZ1 receptor preferentially with a high affinity ratio of the α1/α5 subunits. This selective binding of zolpidem on the BZ1 receptor is not absolute, but it may explain the relative absence of myorelaxant and anticonvulsant effects in animal studies as well as the preservation of deep sleep in human studies of zolpidem tartrate at hypnotic doses.
CNS Activity
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2095172 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | AMBIEN Approved UseAmbien (zolpidem tartrate) is indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation. Ambien has been shown to decrease sleep latency for up to 35 days in controlled clinical studies [see Clinical Studies (14) Launch Date1992 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
121 ng/mL |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
ZOLPIDEM unknown | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
59 ng/mL |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
ZOLPIDEM unknown | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2.5 h |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
ZOLPIDEM unknown | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
26 h |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
ZOLPIDEM unknown | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
7.5% |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
ZOLPIDEM unknown | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
7.5% |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
ZOLPIDEM unknown | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
0.5 mg/kg single, oral Highest studied dose Dose: 0.5 mg/kg Route: oral Route: single Dose: 0.5 mg/kg Sources: |
unhealthy, 2 - 12 years n = 65 Health Status: unhealthy Condition: sleep disturbances Age Group: 2 - 12 years Sex: M+F Population Size: 65 Sources: |
Other AEs: Psychiatric symptom, Gastrointestinal disorder (NOS)... Other AEs: Psychiatric symptom (6 patients) Sources: Gastrointestinal disorder (NOS) (6 patients) Nervous system disorder NOS (5 patients) |
300 mg single, oral Overdose |
unhealthy, 68 years n = 1 Health Status: unhealthy Condition: sleep disturbances Age Group: 68 years Sex: F Population Size: 1 Sources: |
Disc. AE: Death... AEs leading to discontinuation/dose reduction: Death (grade 5, 1 patient) Sources: |
50 mg 1 times / day steady, oral (max) Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: |
unhealthy, adult n = 1959 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 1959 Sources: |
Disc. AE: Drowsiness, Vertigo... AEs leading to discontinuation/dose reduction: Drowsiness (1.1%) Sources: Vertigo (0.8%) Amnesia (0.5%) Nausea (0.5%) Headache (0.4%) Fall (0.4%) |
90 mg 1 times / day steady, oral (max) Highest studied dose Dose: 90 mg, 1 times / day Route: oral Route: steady Dose: 90 mg, 1 times / day Sources: |
unhealthy, adult n = 1701 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 1701 Sources: |
Disc. AE: Drowsiness, Dizziness... AEs leading to discontinuation/dose reduction: Drowsiness (0.5%) Sources: Dizziness (0.4%) Headache (0.5%) Nausea (0.6%) Vomiting (0.5%) |
600 mg single, oral Overdose |
unhealthy, adult n = 344 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 344 Sources: |
Disc. AE: Death... AEs leading to discontinuation/dose reduction: Death (grade 5, 10 patients) Sources: |
600 mg single, oral Overdose |
unhealthy, adult n = 54 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 54 Sources: |
Disc. AE: Somnolence, Coma... AEs leading to discontinuation/dose reduction: Somnolence (100%) Sources: Coma (1 patient) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Nervous system disorder NOS | 5 patients | 0.5 mg/kg single, oral Highest studied dose Dose: 0.5 mg/kg Route: oral Route: single Dose: 0.5 mg/kg Sources: |
unhealthy, 2 - 12 years n = 65 Health Status: unhealthy Condition: sleep disturbances Age Group: 2 - 12 years Sex: M+F Population Size: 65 Sources: |
| Gastrointestinal disorder (NOS) | 6 patients | 0.5 mg/kg single, oral Highest studied dose Dose: 0.5 mg/kg Route: oral Route: single Dose: 0.5 mg/kg Sources: |
unhealthy, 2 - 12 years n = 65 Health Status: unhealthy Condition: sleep disturbances Age Group: 2 - 12 years Sex: M+F Population Size: 65 Sources: |
| Psychiatric symptom | 6 patients | 0.5 mg/kg single, oral Highest studied dose Dose: 0.5 mg/kg Route: oral Route: single Dose: 0.5 mg/kg Sources: |
unhealthy, 2 - 12 years n = 65 Health Status: unhealthy Condition: sleep disturbances Age Group: 2 - 12 years Sex: M+F Population Size: 65 Sources: |
| Death | grade 5, 1 patient Disc. AE |
300 mg single, oral Overdose |
unhealthy, 68 years n = 1 Health Status: unhealthy Condition: sleep disturbances Age Group: 68 years Sex: F Population Size: 1 Sources: |
| Fall | 0.4% Disc. AE |
50 mg 1 times / day steady, oral (max) Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: |
unhealthy, adult n = 1959 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 1959 Sources: |
| Headache | 0.4% Disc. AE |
50 mg 1 times / day steady, oral (max) Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: |
unhealthy, adult n = 1959 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 1959 Sources: |
| Amnesia | 0.5% Disc. AE |
50 mg 1 times / day steady, oral (max) Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: |
unhealthy, adult n = 1959 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 1959 Sources: |
| Nausea | 0.5% Disc. AE |
50 mg 1 times / day steady, oral (max) Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: |
unhealthy, adult n = 1959 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 1959 Sources: |
| Vertigo | 0.8% Disc. AE |
50 mg 1 times / day steady, oral (max) Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: |
unhealthy, adult n = 1959 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 1959 Sources: |
| Drowsiness | 1.1% Disc. AE |
50 mg 1 times / day steady, oral (max) Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: |
unhealthy, adult n = 1959 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 1959 Sources: |
| Dizziness | 0.4% Disc. AE |
90 mg 1 times / day steady, oral (max) Highest studied dose Dose: 90 mg, 1 times / day Route: oral Route: steady Dose: 90 mg, 1 times / day Sources: |
unhealthy, adult n = 1701 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 1701 Sources: |
| Drowsiness | 0.5% Disc. AE |
90 mg 1 times / day steady, oral (max) Highest studied dose Dose: 90 mg, 1 times / day Route: oral Route: steady Dose: 90 mg, 1 times / day Sources: |
unhealthy, adult n = 1701 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 1701 Sources: |
| Headache | 0.5% Disc. AE |
90 mg 1 times / day steady, oral (max) Highest studied dose Dose: 90 mg, 1 times / day Route: oral Route: steady Dose: 90 mg, 1 times / day Sources: |
unhealthy, adult n = 1701 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 1701 Sources: |
| Vomiting | 0.5% Disc. AE |
90 mg 1 times / day steady, oral (max) Highest studied dose Dose: 90 mg, 1 times / day Route: oral Route: steady Dose: 90 mg, 1 times / day Sources: |
unhealthy, adult n = 1701 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 1701 Sources: |
| Nausea | 0.6% Disc. AE |
90 mg 1 times / day steady, oral (max) Highest studied dose Dose: 90 mg, 1 times / day Route: oral Route: steady Dose: 90 mg, 1 times / day Sources: |
unhealthy, adult n = 1701 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 1701 Sources: |
| Death | grade 5, 10 patients Disc. AE |
600 mg single, oral Overdose |
unhealthy, adult n = 344 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 344 Sources: |
| Coma | 1 patient Disc. AE |
600 mg single, oral Overdose |
unhealthy, adult n = 54 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 54 Sources: |
| Somnolence | 100% Disc. AE |
600 mg single, oral Overdose |
unhealthy, adult n = 54 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 54 Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| weak [IC50 99 uM] | ||||
| weak | ||||
| weak |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | yes (co-administration study) Comment: A single-dose interaction study with zolpidem tartrate 10 mg and rifampin (CYP3A4 inducer) 600 mg at steady-state levels in female subjects showed significant reductions of the AUC (-73%), Cmax (-58%), and T1/2 (-36 %) of zolpidem together |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Zolpidem metabolism in vitro: responsible cytochromes, chemical inhibitors, and in vivo correlations. | 1999 Jul |
|
| Acute zolpidem overdose--report of two cases. | 1999 Oct |
|
| Mice lacking the long splice variant of the gamma 2 subunit of the GABA(A) receptor are more sensitive to benzodiazepines. | 2000 Jun |
|
| WHO Expert Committee on Drug Dependence. Thirty-second report. | 2001 |
|
| Development and modulation of GABA(A) receptor-mediated neurotransmission in the CA1 region of prenatally protein malnourished rats. | 2001 |
|
| [Correction of sleep disorders and efficacy of antihypertensive monotherapy in elderly patients: use of ivadal]. | 2001 |
|
| [Zolpidem (ivadal) treatment of sleep disorders]. | 2001 |
|
| Measurement of cerebral perfusion after zolpidem administration in the baboon model. | 2001 |
|
| Type A gamma-aminobutyric acid (GABAA) receptor subunits and benzodiazepine binding: significance to clinical syndromes and their treatment. | 2001 |
|
| Consequences of insomnia and its therapies. | 2001 |
|
| Identification of amino acid residues responsible for the alpha5 subunit binding selectivity of L-655,708, a benzodiazepine binding site ligand at the GABA(A) receptor. | 2001 Apr |
|
| Different types of GABA(A) receptors may mediate the anticonflict and response rate-decreasing effects of zaleplon, zolpidem, and midazolam in squirrel monkeys. | 2001 Aug |
|
| Comparative effects of melatonin, zolpidem and diazepam on sleep, body temperature, blood pressure and heart rate measured by radiotelemetry in Wistar rats. | 2001 Aug |
|
| Zolpidem use and hip fractures in older people. | 2001 Dec |
|
| Hypnotic dependence: zolpidem and zopiclone too. | 2001 Feb |
|
| [Benzodiazepines and benzodiazepine receptor agonists in the treatment of sleep disorders--importance and dangers. Evaluation from the clinical medical view]. | 2001 Jan |
|
| [Drug for the treatment of sleep disorders--review]. | 2001 Jan |
|
| Implications of hypnotic flexibility on patterns of clinical use. | 2001 Jan |
|
| Effectiveness and tolerability of melatonin and zolpidem for the alleviation of jet lag. | 2001 Jul |
|
| [3H]Ro 15-1788 binding sites to brain membrane of the saltwater Mugil cephalus. | 2001 Mar |
|
| GABA(A) receptor alpha1 subunit deletion prevents developmental changes of inhibitory synaptic currents in cerebellar neurons. | 2001 May 1 |
|
| A double-blind comparative study of zolpidem versus zopiclone in the treatment of chronic primary insomnia. | 2001 May-Jun |
|
| Toxicity of alpidem, a peripheral benzodiazepine receptor ligand, but not zolpidem, in rat hepatocytes: role of mitochondrial permeability transition and metabolic activation. | 2001 Nov |
|
| Arousal from a semi-comatose state on zolpidem. | 2001 Oct |
|
| Prevalence between different alpha subunits performing the benzodiazepine binding sites in native heterologous GABA(A) receptors containing the alpha2 subunit. | 2001 Oct |
|
| Prediction of human hepatic clearance from in vivo animal experiments and in vitro metabolic studies with liver microsomes from animals and humans. | 2001 Oct |
|
| Potency of positive gamma-aminobutyric acid(A) modulators to substitute for a midazolam discriminative stimulus in untreated monkeys does not predict potency to attenuate a flumazenil discriminative stimulus in diazepam-treated monkeys. | 2001 Sep |
|
| Zolpidem in restless legs syndrome. | 2002 |
|
| Tolerability of hypnosedatives in older patients. | 2002 |
|
| Hallucinations and Zolpidem. | 2002 Aug |
|
| [Pharmacological profile and clinical effect of zolpidem (Myslee tablets), a hypnotic agent]. | 2002 Feb |
|
| Discriminative stimulus effects of benzodiazepine (BZ)(1) receptor-selective ligands in rhesus monkeys. | 2002 Feb |
|
| [Epileptic seizures as a sign of abstinence from chronic consumption of zolpidem]. | 2002 Feb 1-15 |
|
| Mechanism of alpha-subunit selectivity of benzodiazepine pharmacology at gamma-aminobutyric acid type A receptors. | 2002 Feb 15 |
|
| Fibromyalgia: patient perspectives on symptoms, symptom management, and provider utilization. | 2002 Jan |
|
| Continuous versus non-nightly use of zolpidem in chronic insomnia: results of a large-scale, double-blind, randomized, outpatient study. | 2002 Jan |
|
| Comparative meta-analysis of pharmacotherapy and behavior therapy for persistent insomnia. | 2002 Jan |
|
| Early cerebral activities of the environmental estrogen bisphenol A appear to act via the somatostatin receptor subtype sst(2). | 2002 Jun |
|
| Zolpidem, vascular headache, and hallucinations in an adolescent. | 2002 Jun |
|
| "As needed" pharmacotherapy combined with stimulus control treatment in chronic insomnia--assessment of a novel intervention strategy in a primary care setting. | 2002 Mar |
|
| The effect of zolpidem on operant behavior and its relation to pharmacokinetics after intravenous and subcutaneous administration: concentration-effect relations. | 2002 Mar |
|
| Soyka M, Bottlender R, Möller H-J; Epidemiological evidence for a low abuse potential of zolpidem; Pharmacopsychiatry 2000, 33: 138 - 141. | 2002 Mar |
|
| Selective actions on sleep or anxiety by exploiting GABA-A/benzodiazepine receptor subtypes. | 2002 Mar |
|
| Zolpidem in progressive supranuclear palsy. | 2002 Mar |
|
| Sleep disorders and daytime sleepiness in state police shiftworkers. | 2002 Mar-Apr |
|
| Clinical syndrome associated with zolpidem ingestion in dogs: 33 cases (January 1998-July 2000). | 2002 Mar-Apr |
|
| Role of GABAA/benzodiazepine receptors containing alpha 1 and alpha 5 subunits in the discriminative stimulus effects of triazolam in squirrel monkeys. | 2002 May |
|
| Selective modulation of tonic and phasic inhibitions in dentate gyrus granule cells. | 2002 May |
|
| Adaptive time-frequency parametrization in pharmaco EEG. | 2002 May 30 |
|
| Functional characterization of GABA(A) receptors in neonatal hypothalamic brain slice. | 2002 Oct |
Patents
Sample Use Guides
Dosage in Adults: the recommended initial dose is 5 mg for women and either 5 or 10 mg for men, taken only once per night immediately before bedtime with at least 7-8 hours remaining before the planned time of awakening. If the 5 mg dose is not effective, the dose can be increased to 10 mg. In some patients, the higher morning blood levels following use of the 10 mg dose increase the risk of next day impairment of driving and other activities that require full alertness. The total dose of AMBIEN (zolpidem tartrate) should not exceed 10 mg once daily immediately before bedtime. Ambien should be taken as a single dose and should not be readministered during the same night.
Route of Administration:
Oral
Human embryonic kidney (HEK) 293 cells stably expressing recombinant α1β2γ2s GABA(A) receptors were exposed to zolpidem (1 and 10 μmol/L) for short-term (2 h daily for 1, 2, or 3 consecutive days) or long-term (continuously for 48 h). Radioligand binding studies were used to determine the parameters of [(3)H]flunitrazepam binding sites. A single (2 h) or repeated (2 h daily for 2 or 3 d) short-term exposure to zolpidem affected neither the maximum number of [(3)H]flunitrazepam binding sites nor the affinity. In both control and short-term zolpidem treated groups, addition of GABA (1 nmol/L-1 mmol/L) enhanced [(3)H]flunitrazepam binding in a concentration-dependent manner. The maximum enhancement of [(3)H]flunitrazepam binding in short-term zolpidem treated group was not significantly different from that in the control group. In contrast, long-term exposure to zolpidem resulted in significantly increase in the maximum number of [(3)H]flunitrazepam binding sites without changing the affinity. Furthermore, long-term exposure to zolpidem significantly decreased the ability of GABA to stimulate [(3)H]flunitrazepam binding.
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Systematic Name | English |
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299397-15-2
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18004031
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100000174219
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5XT3YJT4W8
Created by
admin on Sat Dec 16 18:48:00 GMT 2023 , Edited by admin on Sat Dec 16 18:48:00 GMT 2023
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ACTIVE MOIETY
SUBSTANCE RECORD
