ESTAZOLAM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H11ClN4
Molecular Weight	294.738
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ClC1=CC2=C(C=C1)N3C=NN=C3CN=C2C4=CC=CC=C4

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	294.738
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.drugbank.ca/drugs/DB01215
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; anion channel 202 Target ID: CHEMBL2093872 Sources: http://www.drugbank.ca/drugs/DB01215	Agonist 2662
platelet aggregation 75 Target ID: GO:0070527 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2890779	Inhibitor 8228		3.8 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Insomnia 108 Sources: https://www.drugs.com/dosage/estazolam.html	Primary		Approved 8360	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

C_max

Value	Dose	Analyte	Population
54.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1968715/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1968715/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2862746/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2862746/	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

Value	Dose	Analyte	Population
1050 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1968715/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1968715/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2862746/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2862746/	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

T_1/2

Value	Dose	Analyte	Population
14.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1968715/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1968715/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2862746/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2862746/	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/1972381/	healthy, 21-47 n = 60 Health Status: healthy Age Group: 21-47 Sex: M+F Population Size: 60 Sources: https://pubmed.ncbi.nlm.nih.gov/1972381/	Sources: https://pubmed.ncbi.nlm.nih.gov/1972381/
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: https://pubmed.ncbi.nlm.nih.gov/1968713/	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: https://pubmed.ncbi.nlm.nih.gov/1968713/	Disc. AE: Illness, Somnolence... AEs leading to discontinuation/dose reduction: Illness Somnolence (grade 1-2) Dizziness (grade 1-2) Sources: https://pubmed.ncbi.nlm.nih.gov/1968713/
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: https://www.accessdata.fda.gov/drugsatfda_docs/anda/97/74826ap.pdf	unknown, unknown Health Status: unknown Age Group: unknown Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/97/74826ap.pdf	Disc. AE: Somnolence, Respiratory depression... AEs leading to discontinuation/dose reduction: Somnolence Respiratory depression Confusion Coordination impaired Slurred speech Coma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/97/74826ap.pdf

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/1968713/	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: https://pubmed.ncbi.nlm.nih.gov/1968713/
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: https://pubmed.ncbi.nlm.nih.gov/1968713/	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: https://pubmed.ncbi.nlm.nih.gov/1968713/
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: https://pubmed.ncbi.nlm.nih.gov/1968713/	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: https://pubmed.ncbi.nlm.nih.gov/1968713/
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: https://www.accessdata.fda.gov/drugsatfda_docs/anda/97/74826ap.pdf	unknown, unknown Health Status: unknown Age Group: unknown Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/97/74826ap.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/anda/97/74826ap.pdf	unknown, unknown Health Status: unknown Age Group: unknown Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/97/74826ap.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/anda/97/74826ap.pdf	unknown, unknown Health Status: unknown Age Group: unknown Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/97/74826ap.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/anda/97/74826ap.pdf	unknown, unknown Health Status: unknown Age Group: unknown Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/97/74826ap.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/anda/97/74826ap.pdf	unknown, unknown Health Status: unknown Age Group: unknown Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/97/74826ap.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/anda/97/74826ap.pdf	unknown, unknown Health Status: unknown Age Group: unknown Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/97/74826ap.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709 inducer 768	substrate 1010 inhibitor 1752	substrate 1193 inhibitor 1837

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2A6 704 CYP2C19 1463 CYP2E1 876 CYP3A 211 OATP1B1/3 12 OCT1 506	CYP1A2 1032 CYP2A6 523 CYP2C19 985 CYP2E1 648	CYP1A2 689 CYP2B6 538 OCT1 21 P-gp 257 MRP2 111 MRP3 54 BCRP 75 OATP1B1 26

Drug as perpetrator

Target	Modality	Activity
BCRP 765	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
CYP1A2 1673	inhibitor 3240 Sources: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a1e3b4bf-22e9-430a-a768-4d86ae886c9e	no
CYP2A6 736	inhibitor 3240 Sources: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a1e3b4bf-22e9-430a-a768-4d86ae886c9e	no
CYP2B6 985	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
CYP2C19 1537	inhibitor 3240 Sources: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a1e3b4bf-22e9-430a-a768-4d86ae886c9e	no
CYP2C9 1803	inhibitor 3240 Sources: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a1e3b4bf-22e9-430a-a768-4d86ae886c9e	no
CYP2D6 1875	inhibitor 3240 Sources: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a1e3b4bf-22e9-430a-a768-4d86ae886c9e	no
CYP2E1 964	inhibitor 3240 Sources: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a1e3b4bf-22e9-430a-a768-4d86ae886c9e	no
CYP3A 295	inhibitor 3240 Sources: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a1e3b4bf-22e9-430a-a768-4d86ae886c9e	no
CYP3A4 1909	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
MRP2 459	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
MRP3 208	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
OATP1B1 796	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
OCT1 523	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
P-gp 1626	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
OATP1B1/3 12	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/20381614/	yes [Inhibition 10 uM]
OCT1 523	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/20381614/	yes [Inhibition 10 uM]
CYP1A2 1673	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1032	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/16012077/	no
CYP2A6 523	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/16012077/	no
CYP2C19 985	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/16012077/	no
CYP2C9 1010	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/16012077/	no
CYP2D6 1193	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/16012077/	no
CYP2E1 648	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/16012077/	no
CYP3A4 1709	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/16012077/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4858	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4858
ZINC	ZINC000000001370	http://zinc15.docking.org/substances/ZINC000000001370
eMolecules	538014	https://www.emolecules.com/cgi-bin/more?vid=538014

PubMed

Title	Date	PubMed
[Electroencephalographic effects of 450191-S and its metabolites in rabbits with chronic electrode implants].	1986 Jul	3758874
Diazepam-induced decrease in histamine turnover in mouse brain.	1986 May 27	3089825
Metabolic alkalosis and myoclonus from antacid ingestion.	1996 Jun	8835608
[Two complex suicidal poisonings with drugs and their medicolegal aspects].	2001	11450365
Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines.	2002 Apr	11995921
Utilization of psychotropic drugs in Taiwan: an overview of outpatient sector in 2000.	2002 Aug	12455808
[Identification of estazolam, alprazolam and triazolam in human urine by LC/MSn].	2002 Feb	12579961
[The application of a broard spectrum automatic rapid drug identification system in acute drug poisoning].	2002 Jun	12137605
No effect of itraconazole on the single oral dose pharmacokinetics and pharmacodynamics of estazolam.	2002 Jun	12021628
Determination of estazolam in plasma by high-performance liquid chromatography with solid-phase extraction.	2002 May	12036118
Determination of hypnotic benzodiazepines (alprazolam, estazolam, and midazolam) and their metabolites in rat hair and plasma by reversed-phase liquid-chromatography with electrospray ionization mass spectrometry.	2003 Jan 15	12485719
Treatment of phlegm- and heat-induced insomnia by acupuncture in 120 cases.	2003 Mar	12747205
Design and synthesis of 4H-3-(2-phenoxy)phenyl-1,2,4-triazole derivatives as benzodiazepine receptor agonists.	2003 Mar 6	12538007
Effects of the CYP2C19 genotype and cigarette smoking on the single oral dose pharmacokinetics and pharmacodynamics of estazolam.	2003 May	12691790
Date-rape drugs scene in Poland.	2005	16225127
Safety and tolerability of oral antifungal agents in the treatment of fungal nail disease: a proven reality.	2005 Dec	18360572
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Design and synthesis of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles as benzodiazepine receptor agonists.	2005 Jun 15	15876530
TCM treatment for 63 cases of senile dyssomnia.	2005 Mar	15889523
Identification of human cytochrome P450 enzymes involved in the formation of 4-hydroxyestazolam from estazolam.	2005 May	16012077
Sleep maintenance insomnia: strengths and weaknesses of current pharmacologic therapies.	2006 Jan-Mar	16517453
[Analysis of 37 drugs in whole blood by HPLC after solid phase extraction].	2006 Oct 15	17190147
Indiplon in the treatment of sleep disorders.	2007 Dec	19300612
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	17222591
Comparative bioavailability of two estazolam tablet formulations in Indonesian healthy volunteers.	2008	19025059
Abdominal acupuncture for insomnia in women: a randomized controlled clinical trial.	2008	18672743
High performance liquid chromatography-tandem mass spectrometric determination of rupatadine in human plasma and its pharmacokinetics.	2008 Aug 5	18472381
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	18384064
Auricular acupuncture for insomnia: a systematic review.	2008 Nov	18754807
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	18937304
[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	19548433
Drugs associated with more suicidal ideations are also associated with more suicide attempts.	2009 Oct 2	19798416
The XIA's No. 1 sleeping Prescription for the treatment of insomnia of the deficiency type: a clinical observation of 60 cases.	2009 Sep	19894388
Pharmacology of ramelteon, a selective MT1/MT2 receptor agonist: a novel therapeutic drug for sleep disorders.	2009 Winter	19228178
5-(4-Chloro-phen-yl)-3-(2,4-dimethyl-thiazol-5-yl)-1,2,4-triazolo[3,4-a]isoquinoline.	2010 Apr 10	21579114
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443
Management of tinea capitis in childhood.	2010 Jul 14	21437064

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 `Wed Jul 05 22:53:53 UTC 2023` Edited by `admin` on `Wed Jul 05 22:53:53 UTC 2023`
Record UNII	36S3EQV54C
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ESTAZOLAM

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 [WHO-DD]

Common Name

English

ESTAZOLAM CIV [USP-RS]

Common Name

English

ESTAZOLAM [JAN]

Common Name

English

ESTAZOLAM CIV

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