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
Molecular Formula | C19H21N3O |
Molecular Weight | 307.3895 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | ClH |
Molecular Weight | 36.461 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
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 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22922343 |
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 |
|
[Development of drug withdrawal delirium after dependence on zolpidem and zoplicone]. | 1999 Nov |
|
Acute zolpidem overdose--report of two cases. | 1999 Oct |
|
Benztropine for venlafaxine-induced night sweats. | 2000 Apr |
|
[Zolpidem (ivadal) treatment of sleep disorders]. | 2001 |
|
Measurement of cerebral perfusion after zolpidem administration in the baboon model. | 2001 |
|
Future directions in the management of insomnia. | 2001 |
|
Melatonin for preventing and treating jet lag. | 2001 |
|
The acute effects of zolpidem compared to diazepam and lorazepam using radiotelemetry. | 2001 Apr |
|
Zolpidem for antipsychotic-induced parkinsonism. | 2001 Apr |
|
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 abuse. | 2001 Aug |
|
Ribozyme-mediated reduction of the GABA(A) receptor alpha1 subunit. | 2001 Aug 15 |
|
[Zolpidem: the risk of tolerance and dependence according to case reports, systematic studies and recent molecularbiological data]. | 2001 Dec |
|
Hypnotic dependence: zolpidem and zopiclone too. | 2001 Feb |
|
Triazolam discrimination in squirrel monkeys distinguishes high-efficacy agonists from other benzodiazepines and non-benzodiazepine drugs. | 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 |
|
A structure-activity relationship study of the affinity of selected imidazo[1,2-a]pyridine derivatives, congeners of zolpidem, for the omega 1-subtype of the benzodiazepine receptor. | 2001 Jan-Feb |
|
Effectiveness and tolerability of melatonin and zolpidem for the alleviation of jet lag. | 2001 Jul |
|
[Homeopathic specialties as substitutes for benzodiazepines: double-blind vs. placebo study]. | 2001 Jul-Aug |
|
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. | 2001 May |
|
Arousal from a semi-comatose state on zolpidem. | 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 |
|
Melatonin for the prevention and treatment of jet lag. | 2002 |
|
Severe impairment of NMDA receptor function in mice carrying targeted point mutations in the glycine binding site results in drug-resistant nonhabituating hyperactivity. | 2002 Aug 1 |
|
The heterogeneity of central benzodiazepine receptor subtypes in the human hippocampal formation, frontal cortex and cerebellum using [3H]flumazenil and zolpidem. | 2002 Aug 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 |
|
Imaging the GABA-benzodiazepine receptor subtype containing the alpha5-subunit in vivo with [11C]Ro15 4513 positron emission tomography. | 2002 Jul |
|
[Abuse, tolerance and dependence of zolpidem: three case reports]. | 2002 Jul-Aug |
|
"As needed" pharmacotherapy combined with stimulus control treatment in chronic insomnia--assessment of a novel intervention strategy in a primary care setting. | 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 |
|
Long term benzodiazepine use for insomnia in patients over the age of 60: discordance of patient and physician perceptions. | 2002 May 8 |
|
Relation between discriminative and reinforcing effects of midazolam, pentobarbital, chlordiazepoxide, zolpidem, and imidazenil in baboons. | 2002 Oct |
|
Functional characterization of GABA(A) receptors in neonatal hypothalamic brain slice. | 2002 Oct |
|
Zolpidem pharmacokinetic properties in young females: influence of smoking and oral contraceptive use. | 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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22922343
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.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 18:47:59 GMT 2023
by
admin
on
Sat Dec 16 18:47:59 GMT 2023
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Record UNII |
5XT3YJT4W8
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Record Status |
Validated (UNII)
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Record Version |
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299397-15-2
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18004031
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100000174219
Created by
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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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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |
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