ZOLPIDEM TARTRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	2C19H21N3O.C4H6O6
Molecular Weight	764.8659
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.CN(C)C(=O)CC1=C(N=C2C=CC(C)=CN12)C3=CC=C(C)C=C3.CN(C)C(=O)CC4=C(N=C5C=CC(C)=CN45)C6=CC=C(C)C=C6

InChI

InChIKey=VXRDAMSNTXUHFX-CEAXSRTFSA-N

InChI=1S/2C19H21N3O.C4H6O6/c2*1-13-5-8-15(9-6-13)19-16(11-18(23)21(3)4)22-12-14(2)7-10-17(22)20-19;5-1(3(7)8)2(6)4(9)10/h2*5-10,12H,11H2,1-4H3;1-2,5-6H,(H,7,8)(H,9,10)/t;;1-,2-/m..1/s1

HIDE SMILES / InChI

Molecular Formula	C4H6O6
Molecular Weight	150.0868
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

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

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019908s038lbl.pdf

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
GABA-A receptor; alpha-1/beta-2/gamma-2 27 Target ID: CHEMBL2095172 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22922343	Positive Allosteric Modulator 179

Conditions

Condition	Modality	Targets	Highest Phase	Product
Insomnia 108 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019908s038lbl.pdf	Primary		Approved 8429	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

C_max

Value	Dose	Co-administered	Analyte	Population
121 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019908s027lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019908s027lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019908s027lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019908s027lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
7.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019908s027lbl.pdf	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% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019908s027lbl.pdf	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: https://pubmed.ncbi.nlm.nih.gov/17957186/	unhealthy, 2 - 12 years n = 65 Health Status: unhealthy Condition: sleep disturbances Age Group: 2 - 12 years Sex: M+F Population Size: 65 Sources: https://pubmed.ncbi.nlm.nih.gov/17957186/	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: https://pubmed.ncbi.nlm.nih.gov/17957186/
300 mg single, oral Overdose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8635759/	unhealthy, 68 years n = 1 Health Status: unhealthy Condition: sleep disturbances Age Group: 68 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/8635759/	Disc. AE: Death... AEs leading to discontinuation/dose reduction: Death (grade 5, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/8635759/
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019908s035,021774s016lbl.pdf	unhealthy, adult n = 1959 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 1959 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019908s035,021774s016lbl.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019908s035,021774s016lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019908s035,021774s016lbl.pdf	unhealthy, adult n = 1701 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 1701 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019908s035,021774s016lbl.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019908s035,021774s016lbl.pdf
600 mg single, oral Overdose Dose: 600 mg Route: oral Route: single Dose: 600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10517569/	unhealthy, adult n = 344 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 344 Sources: https://pubmed.ncbi.nlm.nih.gov/10517569/	Disc. AE: Death... AEs leading to discontinuation/dose reduction: Death (grade 5, 10 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/10517569/
600 mg single, oral Overdose Dose: 600 mg Route: oral Route: single Dose: 600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8693299/	unhealthy, adult n = 54 Health Status: unhealthy Condition: sleep disturbances Age Group: adult Sex: unknown Population Size: 54 Sources: https://pubmed.ncbi.nlm.nih.gov/8693299/	Disc. AE: Somnolence, Coma... AEs leading to discontinuation/dose reduction: Somnolence (100%) Coma (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/8693299/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	inhibitor 1767 substrate 1037	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C19 1478 CYP3A 214 P-gp 1461	CYP1A2 1054 CYP2C19 991

Drug as perpetrator

Target	Modality	Activity
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12469329/	no
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12469329/	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12469329/	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12469329/	no
CYP3A 298	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12469329/	weak [IC50 99 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12469329/	weak
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12469329/	weak

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10383565/	yes
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10383565/	yes
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10383565/	yes
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10383565/	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10383565/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019908s037lbl.pdf	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 Sources: https://pubmed.ncbi.nlm.nih.gov/10383565/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019908s037lbl.pdf

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/23061993/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:10125	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:10125
ChemicalBook	CB14188703	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB14188703
ChemicalBook	CB44188704	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB44188704
ChemicalBook	CB83360349	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB83360349
ChemicalBook	CB84188702	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB84188702
ZINC	ZINC000000003876	http://zinc15.docking.org/substances/ZINC000000003876
eMolecules	596284	https://www.emolecules.com/cgi-bin/more?vid=596284

PubMed

Title	Date	PubMed
Zolpidem metabolism in vitro: responsible cytochromes, chemical inhibitors, and in vivo correlations.	1999 Jul	10383565
Extraordinary arousal from semi-comatose state on zolpidem. A case report.	2000 Jan	10721397
WHO Expert Committee on Drug Dependence. Thirty-second report.	2001	11851193
A psychiatric perspective on insomnia.	2001	11388587
Melatonin for preventing and treating jet lag.	2001	11279722
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	11498724
Delirium associated with zolpidem.	2001 Dec	11793620
[Zolpidem: the risk of tolerance and dependence according to case reports, systematic studies and recent molecularbiological data].	2001 Dec	11753748
Hypnotic dependence: zolpidem and zopiclone too.	2001 Feb	11503851
Implications of hypnotic flexibility on patterns of clinical use.	2001 Jan	11219327
[Homeopathic specialties as substitutes for benzodiazepines: double-blind vs. placebo study].	2001 Jul-Aug	11677862
gamma-Aminobutyric acid(A) receptor subunit expression predicts functional changes in hippocampal dentate granule cells during postnatal development.	2001 Jun	11389177
GABA(A) receptor alpha1 subunit deletion prevents developmental changes of inhibitory synaptic currents in cerebellar neurons.	2001 May 1	11312285
Arousal from a semi-comatose state on zolpidem.	2001 Oct	11732448
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	12151550
The heterogeneity of central benzodiazepine receptor subtypes in the human hippocampal formation, frontal cortex and cerebellum using [3H]flumazenil and zolpidem.	2002 Aug 15	12225875
[Pharmacological profile and clinical effect of zolpidem (Myslee tablets), a hypnotic agent].	2002 Feb	11862759
Zolpidem improves dystonia in "Lubag" or X-linked dystonia-parkinsonism syndrome.	2002 Feb 26	11865155
Fibromyalgia: patient perspectives on symptoms, symptom management, and provider utilization.	2002 Jan	11839925
Imaging the GABA-benzodiazepine receptor subtype containing the alpha5-subunit in vivo with [11C]Ro15 4513 positron emission tomography.	2002 Jul	12142573
Rifampin and rifabutin drug interactions: an update.	2002 May 13	11996607
Long term benzodiazepine use for insomnia in patients over the age of 60: discordance of patient and physician perceptions.	2002 May 8	12019038
Relation between discriminative and reinforcing effects of midazolam, pentobarbital, chlordiazepoxide, zolpidem, and imidazenil in baboons.	2002 Oct	12373448
Zolpidem pharmacokinetic properties in young females: influence of smoking and oral contraceptive use.	2002 Oct	12362929
Mechanisms of anabolic androgenic steroid modulation of alpha(1)beta(3)gamma(2L) GABA(A) receptors.	2002 Sep	12367607

Patents

Sample Use Guides

In Vivo Use Guide

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

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 `Fri Dec 15 15:11:16 GMT 2023` Edited by `admin` on `Fri Dec 15 15:11:16 GMT 2023`
Record UNII	WY6W63843K
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ZOLPIDEM TARTRATE

Official Name

English

(2R,3R)-2,3-DIHYDROXYSUCCINIC ACID - N,N-DIMETHYL-2-(6-METHYL-2-(4-METHYLPHENYL)IMIDAZO(1,2-A)PYRIDIN-3-YL)ACETAMIDE (1:2)

Common Name

English

AMBIEN

Brand Name

English

STILNOX

Brand Name

English

ZOLPIDEM TARTRATE [MART.]

Common Name

English

SL-80.0750

Code

English

N,N,6-TRIMETHYL-2-P-TOLYL-IMIDAZO(1,2-A)PYRIDINE-3-ACETAMIDE L-(+)-HEMITARTRATE (2:1)

Common Name

English

Zolpidem tartrate [WHO-DD]

Common Name

English

ZOLPIDEM TARTRATE CIV

Common Name

English

ZOLPIDEM HEMITARTRATE

Common Name

English

N,N,6-TRIMETHYL-2-P-TOLYLIMIDAZO(1,2-A)PYRIDINE-3-ACETAMIDE L-(+)-TARTRATE (2:1)

Common Name

English

ZOLPIDEM L-(+)-HEMITARTRATE [MI]

Common Name

English

MYSLEE

Brand Name

English

ZOLPIDEM TARTRATE [ORANGE BOOK]

Common Name

English

INTERMEZZO

Brand Name

English

IVADAL

Brand Name

English

ZOLPIDEM TARTRATE [EP MONOGRAPH]

Common Name

English

NIOTAL

Brand Name

English

ZOLPIDEM TARTRATE [USP MONOGRAPH]

Common Name

English

ZOLPIDEM TARTRATE [JAN]

Common Name

English

ZOLPIDEM TARTRATE [USAN]

Common Name

English

SL-80.0750-23N

Code

English

SL 80.0750-23N

Code

English

ZOLPIDEM TARTRATE [HSDB]

Common Name

English

STILNOCT

Brand Name

English

ZOLPIDEM TARTRATE CIV [USP-RS]

Common Name

English

TOVALT

Brand Name

English

IMIDAZO(1,2-A)PYRIDINE-3-ACETAMIDE, N,N,6-TRIMETHYL-2-(4-METHYLPHENYL)-, (R-(R*,R*))-2,3-DIHYDROXYBUTANEDIOATE (2:1)

Common Name

English

ZOLPIDEM L-(+)-HEMITARTRATE

Common Name

English

ZOLPIDEM TARTRATE [VANDF]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29756