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

Details

Stereochemistry ACHIRAL
Molecular Formula C16H11ClN4
Molecular Weight 294.7389
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ESTAZOLAM

SMILES

c1ccc(cc1)C2=NCc3nncn3-c4ccc(cc42)Cl

InChI

InChIKey=CDCHDCWJMGXXRH-UHFFFAOYSA-N
InChI=1S/C16H11ClN4/c17-12-6-7-14-13(8-12)16(11-4-2-1-3-5-11)18-9-15-20-19-10-21(14)15/h1-8,10H,9H2

HIDE SMILES / InChI

Molecular Formula C16H11ClN4
Molecular Weight 294.7389
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugs.com/pro/estazolam.html

Estazolam, a triazolobenzodiazepine derivative, is an oral hypnotic agent with anticonvulsant, hypnotic, and muscle relaxant properties. It has been shown in some cases to be more potent than diazepam or nitrazepam. Benzodiazepines bind nonspecifically to benzodiazepine receptors, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell. Used for the short-term management of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. Marketed under the brand names ProSom, Eurodin.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.8 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Estazolam

Approved Use

Estazolam is indicated for the short-term management of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings.

Launch Date

8.7186237E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
54.7 ng/mL
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
98.6 ng/mL
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
194 ng/mL
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
180 ng/mL
2 mg 2 times / day steady-state, oral
dose: 2 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ESTAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1050 ng × h/mL
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
2060 ng × h/mL
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
4343 ng × h/mL
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
5517 ng × h/mL
2 mg 2 times / day steady-state, oral
dose: 2 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ESTAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
14.9 h
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
14.3 h
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
19 h
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
17 h
2 mg 2 times / day steady-state, oral
dose: 2 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ESTAZOLAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
6 mg 1 times / day single, oral
Highest studied dose
Dose: 6 mg, 1 times / day
Route: oral
Route: single
Dose: 6 mg, 1 times / day
Sources:
healthy, 21-47
n = 60
Health Status: healthy
Age Group: 21-47
Sex: M+F
Population Size: 60
Sources:
2 mg 1 times / day multiple, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 42.9 (18-85)
n = 685
Health Status: unhealthy
Condition: insomnia
Age Group: 42.9 (18-85)
Sex: M+F
Population Size: 685
Sources:
Disc. AE: Illness, Somnolence...
AEs leading to
discontinuation/dose reduction:
Illness
Somnolence (grade 1-2)
Dizziness (grade 1-2)
Sources:
40 mg 1 times / day single, oral
Overdose
Dose: 40 mg, 1 times / day
Route: oral
Route: single
Dose: 40 mg, 1 times / day
Sources:
unknown, unknown
Health Status: unknown
Age Group: unknown
Sex: unknown
Sources:
Disc. AE: Somnolence, Respiratory depression...
AEs leading to
discontinuation/dose reduction:
Somnolence
Respiratory depression
Confusion
Coordination impaired
Slurred speech
Coma
Sources:
AEs

AEs

AESignificanceDosePopulation
Illness Disc. AE
2 mg 1 times / day multiple, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 42.9 (18-85)
n = 685
Health Status: unhealthy
Condition: insomnia
Age Group: 42.9 (18-85)
Sex: M+F
Population Size: 685
Sources:
Dizziness grade 1-2
Disc. AE
2 mg 1 times / day multiple, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 42.9 (18-85)
n = 685
Health Status: unhealthy
Condition: insomnia
Age Group: 42.9 (18-85)
Sex: M+F
Population Size: 685
Sources:
Somnolence grade 1-2
Disc. AE
2 mg 1 times / day multiple, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 42.9 (18-85)
n = 685
Health Status: unhealthy
Condition: insomnia
Age Group: 42.9 (18-85)
Sex: M+F
Population Size: 685
Sources:
Coma Disc. AE
40 mg 1 times / day single, oral
Overdose
Dose: 40 mg, 1 times / day
Route: oral
Route: single
Dose: 40 mg, 1 times / day
Sources:
unknown, unknown
Health Status: unknown
Age Group: unknown
Sex: unknown
Sources:
Confusion Disc. AE
40 mg 1 times / day single, oral
Overdose
Dose: 40 mg, 1 times / day
Route: oral
Route: single
Dose: 40 mg, 1 times / day
Sources:
unknown, unknown
Health Status: unknown
Age Group: unknown
Sex: unknown
Sources:
Coordination impaired Disc. AE
40 mg 1 times / day single, oral
Overdose
Dose: 40 mg, 1 times / day
Route: oral
Route: single
Dose: 40 mg, 1 times / day
Sources:
unknown, unknown
Health Status: unknown
Age Group: unknown
Sex: unknown
Sources:
Respiratory depression Disc. AE
40 mg 1 times / day single, oral
Overdose
Dose: 40 mg, 1 times / day
Route: oral
Route: single
Dose: 40 mg, 1 times / day
Sources:
unknown, unknown
Health Status: unknown
Age Group: unknown
Sex: unknown
Sources:
Slurred speech Disc. AE
40 mg 1 times / day single, oral
Overdose
Dose: 40 mg, 1 times / day
Route: oral
Route: single
Dose: 40 mg, 1 times / day
Sources:
unknown, unknown
Health Status: unknown
Age Group: unknown
Sex: unknown
Sources:
Somnolence Disc. AE
40 mg 1 times / day single, oral
Overdose
Dose: 40 mg, 1 times / day
Route: oral
Route: single
Dose: 40 mg, 1 times / day
Sources:
unknown, unknown
Health Status: unknown
Age Group: unknown
Sex: unknown
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes [Inhibition 10 uM]
yes [Inhibition 10 uM]
yes
Drug as victim
PubMed

PubMed

TitleDatePubMed
[Electroencephalographic effects of 450191-S and its metabolites in rabbits with chronic electrode implants].
1986 Jul
Inhibition of the binding and the behavioral effects of thyrotropin-releasing hormone (TRH) by the triazolobenzodiazepines.
1988 May
Estazolam treatment of insomnia in generalized anxiety disorder: a placebo-controlled study.
1991 Aug
Metabolic alkalosis and myoclonus from antacid ingestion.
1996 Jun
[Identification of estazolam, alprazolam and triazolam in human urine by LC/MSn].
2002 Feb
Simultaneous analyses of hypoglycemic agents and C-peptide are essential in a homicide case with the combined dosing insulin and insulin-releasing drug.
2002 Mar
A study into the rate of incorporation of eight benzodiazepines into rat hair.
2003 Apr 23
Treatment of phlegm- and heat-induced insomnia by acupuncture in 120 cases.
2003 Mar
Effects of the CYP2C19 genotype and cigarette smoking on the single oral dose pharmacokinetics and pharmacodynamics of estazolam.
2003 May
Pharmacokinetics and drug interactions of the sedative hypnotics.
2003 Winter
Overview of the therapeutic management of insomnia with zolpidem.
2004
Simultaneous determination of albendazole and its major active metabolite in human plasma using a sensitive and specific liquid chromatographic-tandem mass spectrometric method.
2004 Jun 29
Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds.
2005
Date-rape drugs scene in Poland.
2005
Safety and tolerability of oral antifungal agents in the treatment of fungal nail disease: a proven reality.
2005 Dec
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Design and synthesis of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles as benzodiazepine receptor agonists.
2005 Jun 15
TCM treatment for 63 cases of senile dyssomnia.
2005 Mar
Identification of human cytochrome P450 enzymes involved in the formation of 4-hydroxyestazolam from estazolam.
2005 May
[Effects of midazolam and estazolam as hypnotics in hypertensive patients with chronic insomnia: a multicentre, open labeled, randomized clinical trial].
2006 Apr
Simultaneous determination of spironolactone and its active metabolite canrenone in human plasma by HPLC-APCI-MS.
2006 Apr
Determination of four benzodiazepine residues in pork using multiwalled carbon nanotube solid-phase extraction and gas chromatography-mass spectrometry.
2006 Dec 8
High-performance liquid chromatography-atmospheric pressure chemical ionisation-mass spectrometry determination of zaleplon in human plasma.
2006 Feb 24
Sleep maintenance insomnia: strengths and weaknesses of current pharmacologic therapies.
2006 Jan-Mar
[Analysis of 37 drugs in whole blood by HPLC after solid phase extraction].
2006 Oct 15
Indiplon in the treatment of sleep disorders.
2007 Dec
[Randomized and controlled study on effect of acupuncture on sleep quality in the patient of primary insomnia].
2007 Dec
[Comparative study on treatment of somnipathy in patients with hypertension by traditional Chinese medicine and by estazolam].
2007 Feb
High performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI) method for simultaneous determination of venlafaxine and its three metabolites in human plasma.
2007 May 1
Sensitive and selective liquid chromatography-tandem mass spectrometry method for the quantification of aniracetam in human plasma.
2007 Oct 15
Comparative bioavailability of two estazolam tablet formulations in Indonesian healthy volunteers.
2008
Abdominal acupuncture for insomnia in women: a randomized controlled clinical trial.
2008
High performance liquid chromatography-tandem mass spectrometric determination of rupatadine in human plasma and its pharmacokinetics.
2008 Aug 5
Long-term stability of various drugs and metabolites in urine, and preventive measures against their decomposition with special attention to filtration sterilization.
2008 Jan 30
Simultaneous determination of naringenin and hesperetin in rats after oral administration of Da-Cheng-Qi decoction by high-performance liquid chromatography-tandem mass spectrometry.
2008 Jul
Auricular acupuncture for insomnia: a systematic review.
2008 Nov
Simultaneous determination of benzodiazepines and their metabolites in human serum by liquid chromatography-tandem mass spectrometry using a high-resolution octadecyl silica column compatible with aqueous compounds.
2009 Apr
[Simultaneous determination of 5 sedative hypnotics in human plasma by reversed phase high-performance liquid chromatography].
2009 Jul
Forty cases of insomnia treated by suspended moxibustion at Baihui (GV 20).
2009 Jun
[Effect of modified xiaoyao powder for improving sleep in patients with psychological stress insomnia].
2009 Mar
[Analysis on somnipathy related factors in elderly patients with stroke and comparative study on the efficacy of treatment by traditional Chinese medicine and by estazolam].
2009 Mar
Algorithms for the assessment and management of insomnia in primary care.
2009 Nov 3
Drugs associated with more suicidal ideations are also associated with more suicide attempts.
2009 Oct 2
The XIA's No. 1 sleeping Prescription for the treatment of insomnia of the deficiency type: a clinical observation of 60 cases.
2009 Sep
Pharmacology of ramelteon, a selective MT1/MT2 receptor agonist: a novel therapeutic drug for sleep disorders.
2009 Winter
Four cases of dysthymic disorder and general malaise successfully treated with traditional herbal (kampo) medicines: kamiuntanto.
2010
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.
2010 Dec
[The influence of estazolam on human neurobehavioral function].
2010 Feb
[Clinical observation on acupoint catgut embedding at head-acupoint combined with massage of sole for treatment of refractory insomnia].
2010 Feb
A validated method for simultaneous screening and quantification of twenty-three benzodiazepines and metabolites plus zopiclone and zaleplone in whole blood by liquid-liquid extraction and ultra-performance liquid chromatography- tandem mass spectrometry.
2010 Jul-Aug
Patents

Sample Use Guides

In Vivo Use Guide
Usual Adult Dose for Insomnia 1 to 2 mg orally at bedtime
Route of Administration: Oral
In Vitro Use Guide
Incubation of rabbit PRP with etizolam for 2 min before administration of aggregating agents inhibited aggregation induced by PAF (190 nM) with an IC50 of 3.8 uM. Etizolam at a higher concentration (300 uM) only slightly in hibited ADP (15 uM) and arachidonic acid-induced aggregation
Substance Class Chemical
Created
by admin
on Sat Jun 26 15:09:12 UTC 2021
Edited
by admin
on Sat Jun 26 15:09:12 UTC 2021
Record UNII
36S3EQV54C
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ESTAZOLAM
INN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
NSC-290818
Code English
ESTAZOLAM [USAN]
Common Name English
ABBOTT-47631
Code English
ESTAZOLAM [VANDF]
Common Name English
ESTAZOLAM [IARC]
Common Name English
ESTAZOLAM [USP MONOGRAPH]
Common Name English
ESTAZOLAM [MI]
Common Name English
ESTAZOLAM CIV [USP-RS]
Common Name English
ESTAZOLAM CIV
USP-RS  
Common Name English
ESTAZOLAM [WHO-DD]
Common Name English
8-CHLORO-6-PHENYL-4H-S-TRIAZOLO(4,3-A)(1,4)BENZODIAZEPINE
Systematic Name English
4H-(1,2,4)TRIAZOLO(4,3-A)(1,4)BENZODIAZEPINE, 8-CHLORO-6-PHENYL-
Systematic Name English
ESTAZOLAM [MART.]
Common Name English
ESTAZOLAM [INN]
Common Name English
PROSOM
Brand Name English
ESTAZOLAM [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1012
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
WHO-ATC N05CD04
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
NDF-RT N0000007542
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
LIVERTOX 371
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
WHO-VATC QN05CD04
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
NDF-RT N0000175694
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
DEA NO. 2756
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C47520
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY
MESH
D004949
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY
PUBCHEM
3261
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY
EVMPD
SUB07241MIG
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY
DRUG CENTRAL
1056
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY
IUPHAR
7550
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY
RXCUI
4077
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY RxNorm
LACTMED
Estazolam
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY
DRUG BANK
DB01215
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY
WIKIPEDIA
ESTAZOLAM
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY
ChEMBL
CHEMBL285674
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY
FDA UNII
36S3EQV54C
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY
INN
3611
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY
ECHA (EC/EINECS)
249-982-4
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY
MERCK INDEX
M5027
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY Merck Index
EPA CompTox
29975-16-4
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY
CAS
29975-16-4
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY
USP_CATALOG
1249905
Created by admin on Sat Jun 26 15:09:13 UTC 2021 , Edited by admin on Sat Jun 26 15:09:13 UTC 2021
PRIMARY USP-RS
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