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

Details

Stereochemistry ACHIRAL
Molecular Formula C19H21N3O.ClH.H2O
Molecular Weight 361.866
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZOLPIDEM HYDROCHLORIDE MONOHYDRATE

SMILES

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

InChI

InChIKey=YELFUPKDSOBFAN-UHFFFAOYSA-N
InChI=1S/C19H21N3O.ClH.H2O/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;1H2

HIDE SMILES / InChI

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

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 H2O
Molecular Weight 18.0153
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
Acute zolpidem overdose--report of two cases.
1999 Oct
Extraordinary arousal from semi-comatose state on zolpidem. A case report.
2000 Jan
[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
A psychiatric perspective on insomnia.
2001
Melatonin for preventing and treating jet lag.
2001
[Comparative study of effects of ivadal and rodedorm in insomnia in structure of borderline mental diseases].
2001
The acute effects of zolpidem compared to diazepam and lorazepam using radiotelemetry.
2001 Apr
Zolpidem for antipsychotic-induced parkinsonism.
2001 Apr
Comparative effects of melatonin, zolpidem and diazepam on sleep, body temperature, blood pressure and heart rate measured by radiotelemetry in Wistar rats.
2001 Aug
Functional analysis of GABA(A) receptors in nucleus tractus solitarius neurons from neonatal rats.
2001 Dec 7
Triazolam discrimination in squirrel monkeys distinguishes high-efficacy agonists from other benzodiazepines and non-benzodiazepine drugs.
2001 Feb
Screening for detection of new antidepressants, neuroleptics, hypnotics, and their metabolites in urine by GC-MS developed using rat liver microsomes.
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
Acute zolpidem overdose leading to coma and respiratory failure.
2001 Jul
[Homeopathic specialties as substitutes for benzodiazepines: double-blind vs. placebo study].
2001 Jul-Aug
gamma-Aminobutyric acid(A) receptor subunit expression predicts functional changes in hippocampal dentate granule cells during postnatal development.
2001 Jun
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
Treatment of insomnia in hospitalized patients.
2001 Nov
Prevalence between different alpha subunits performing the benzodiazepine binding sites in native heterologous GABA(A) receptors containing the alpha2 subunit.
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
Melatonin for the prevention and treatment of jet lag.
2002
[Unexplained increase in aminotransferases and obstructive sleep apnea syndrome].
2002 Apr
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
[Pharmacological profile and clinical effect of zolpidem (Myslee tablets), a hypnotic agent].
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
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
Imaging the GABA-benzodiazepine receptor subtype containing the alpha5-subunit in vivo with [11C]Ro15 4513 positron emission tomography.
2002 Jul
Early cerebral activities of the environmental estrogen bisphenol A appear to act via the somatostatin receptor subtype sst(2).
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
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
GABAA-benzodiazepine receptor complex ligands and stress-induced hyperthermia in singly housed mice.
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
GABA(A) receptor alpha-1 subunit deletion alters receptor subtype assembly, pharmacological and behavioral responses to benzodiazepines and zolpidem.
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 18:56:23 GMT 2023
Edited
by admin
on Sat Dec 16 18:56:23 GMT 2023
Record UNII
HL85PZ374H
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ZOLPIDEM HYDROCHLORIDE MONOHYDRATE
Common Name English
IMIDAZO(1,2-A)PYRIDINE-3-ACETAMIDE, N,N,6-TRIMETHYL-2-(4-METHYLPHENYL)-, MONOHYDROCHLORIDE, MONOHYDRATE
Systematic Name English
IMIDAZO(1,2-A)PYRIDINE-3-ACETAMIDE, N,N,6-TRIMETHYL-2-(4-METHYLPHENYL)-, HYDROCHLORIDE, HYDRATE (1:1:1)
Systematic Name English
Code System Code Type Description
PUBCHEM
18004027
Created by admin on Sat Dec 16 18:56:23 GMT 2023 , Edited by admin on Sat Dec 16 18:56:23 GMT 2023
PRIMARY
FDA UNII
HL85PZ374H
Created by admin on Sat Dec 16 18:56:23 GMT 2023 , Edited by admin on Sat Dec 16 18:56:23 GMT 2023
PRIMARY
CAS
299397-16-3
Created by admin on Sat Dec 16 18:56:23 GMT 2023 , Edited by admin on Sat Dec 16 18:56:23 GMT 2023
PRIMARY
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