U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C19H21N3O.BrH
Molecular Weight 388.301
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZOLPIDEM HYDROBROMIDE

SMILES

Br.CN(C)C(=O)CC1=C(N=C2C=CC(C)=CN12)C3=CC=C(C)C=C3

InChI

InChIKey=ZQPYVWMBTZWNRI-UHFFFAOYSA-N
InChI=1S/C19H21N3O.BrH/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

HIDE SMILES / InChI

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 BrH
Molecular Weight 80.912
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
AMBIEN

Approved Use

Ambien (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 Date

1992
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Funbound

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse 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)
Gastrointestinal disorder (NOS) (6 patients)
Nervous system disorder NOS (5 patients)
Sources:
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources:
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%)
Vertigo (0.8%)
Amnesia (0.5%)
Nausea (0.5%)
Headache (0.4%)
Fall (0.4%)
Sources:
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%)
Dizziness (0.4%)
Headache (0.5%)
Nausea (0.6%)
Vomiting (0.5%)
Sources:
600 mg single, oral
Overdose
Dose: 600 mg
Route: oral
Route: single
Dose: 600 mg
Sources:
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
Dose: 600 mg
Route: oral
Route: single
Dose: 600 mg
Sources:
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%)
Coma (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
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
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources:
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
Dose: 600 mg
Route: oral
Route: single
Dose: 600 mg
Sources:
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
Dose: 600 mg
Route: oral
Route: single
Dose: 600 mg
Sources:
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
Dose: 600 mg
Route: oral
Route: single
Dose: 600 mg
Sources:
unhealthy, adult
n = 54
Health Status: unhealthy
Condition: sleep disturbances
Age Group: adult
Sex: unknown
Population Size: 54
Sources:
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical 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

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Abuse, dependence, and epileptic seizures after zolpidem withdrawal: review and case report.
2000 Sep-Oct
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
Consequences of insomnia and its therapies.
2001
Melatonin for preventing and treating jet lag.
2001
Zolpidem, triazolam, and diazepam decrease distress vocalizations in mouse pups: differential antagonism by flumazenil and beta-Carboline-3-carboxylate-t-butyl ester (beta-CCt).
2001 Apr
Alternative medicine. Achieving balance between herbal remedies and medical therapy.
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
Assessing the effects of an intervention by a pharmacist on prescribing and administration of hypnotics in nursing homes.
2001 Dec
Delirium associated with zolpidem.
2001 Dec
Triazolam discrimination in squirrel monkeys distinguishes high-efficacy agonists from other benzodiazepines and non-benzodiazepine drugs.
2001 Feb
Hormonal responses to exercise after partial sleep deprivation and after a hypnotic drug-induced sleep.
2001 Feb
Implications of hypnotic flexibility on patterns of clinical use.
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
Acute zolpidem overdose leading to coma and respiratory failure.
2001 Jul
Effectiveness and tolerability of melatonin and zolpidem for the alleviation of jet lag.
2001 Jul
gamma-Aminobutyric acid(A) receptor subunit expression predicts functional changes in hippocampal dentate granule cells during postnatal development.
2001 Jun
[3H]Ro 15-1788 binding sites to brain membrane of the saltwater Mugil cephalus.
2001 Mar
Toxicity of alpidem, a peripheral benzodiazepine receptor ligand, but not zolpidem, in rat hepatocytes: role of mitochondrial permeability transition and metabolic activation.
2001 Nov
Prediction of human hepatic clearance from in vivo animal experiments and in vitro metabolic studies with liver microsomes from animals and humans.
2001 Oct
Insomnia: therapeutic approach.
2001 Sep
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
Tolerability of hypnosedatives in older patients.
2002
Hallucinations and Zolpidem.
2002 Aug
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
[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
Changes in GABA(A) receptor gene expression induced by withdrawal of, but not by long-term exposure to, zaleplon or zolpidem.
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
Zolpidem improves dystonia in "Lubag" or X-linked dystonia-parkinsonism syndrome.
2002 Feb 26
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
Soyka M, Bottlender R, Möller H-J; Epidemiological evidence for a low abuse potential of zolpidem; Pharmacopsychiatry 2000, 33: 138 - 141.
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
Anxiolytic-like effects of acute and chronic GABA transporter inhibition in rats.
2002 May
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
GABAA-benzodiazepine receptor complex ligands and stress-induced hyperthermia in singly housed mice.
2002 May
Rifampin and rifabutin drug interactions: an update.
2002 May 13
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
Relative picrotoxin insensitivity distinguishes ionotropic GABA receptor-mediated IPSCs in hippocampal interneurons.
2002 Sep
GABA(A) receptor alpha-1 subunit deletion alters receptor subtype assembly, pharmacological and behavioral responses to benzodiazepines and zolpidem.
2002 Sep
Mechanisms of anabolic androgenic steroid modulation of alpha(1)beta(3)gamma(2L) GABA(A) receptors.
2002 Sep
Patents

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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 19:10:19 GMT 2023
Edited
by admin
on Sat Dec 16 19:10:19 GMT 2023
Record UNII
MW5XV2E6AB
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ZOLPIDEM HYDROBROMIDE
Common Name English
IMIDAZO(1,2-A)PYRIDINE-3-ACETAMIDE, N,N,6-TRIMETHYL-2-(4-METHYLPHENYL)-, HYDROBROMIDE (1:1)
Systematic Name English
IMIDAZO(1,2-A)PYRIDINE-3-ACETAMIDE, N,N,6-TRIMETHYL-2-(4-METHYLPHENYL)-, MONOHYDROBROMIDE
Systematic Name English
Code System Code Type Description
FDA UNII
MW5XV2E6AB
Created by admin on Sat Dec 16 19:10:19 GMT 2023 , Edited by admin on Sat Dec 16 19:10:19 GMT 2023
PRIMARY
PUBCHEM
18004030
Created by admin on Sat Dec 16 19:10:19 GMT 2023 , Edited by admin on Sat Dec 16 19:10:19 GMT 2023
PRIMARY
CAS
299397-23-2
Created by admin on Sat Dec 16 19:10:19 GMT 2023 , Edited by admin on Sat Dec 16 19:10:19 GMT 2023
PRIMARY
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