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 2678
platelet aggregation 76 Target ID: GO:0070527 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2890779	Inhibitor 8297		3.8 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Insomnia 108 Sources: https://www.drugs.com/dosage/estazolam.html	Primary		Approved 8429	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 1997

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 1737 inducer 781	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882 CYP3A 214 OATP1B1/3 12 OCT1 512	CYP1A2 1054 CYP2A6 543 CYP2C19 991 CYP2E1 667	CYP1A2 701 CYP2B6 547 OCT1 35 P-gp 257 MRP2 111 MRP3 53 BCRP 75 OATP1B1 26

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
CYP1A2 1692	inhibitor 3277 Sources: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a1e3b4bf-22e9-430a-a768-4d86ae886c9e	no
CYP2A6 739	inhibitor 3277 Sources: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a1e3b4bf-22e9-430a-a768-4d86ae886c9e	no
CYP2B6 1001	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
CYP2C19 1553	inhibitor 3277 Sources: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a1e3b4bf-22e9-430a-a768-4d86ae886c9e	no
CYP2C9 1819	inhibitor 3277 Sources: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a1e3b4bf-22e9-430a-a768-4d86ae886c9e	no
CYP2D6 1891	inhibitor 3277 Sources: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a1e3b4bf-22e9-430a-a768-4d86ae886c9e	no
CYP2E1 970	inhibitor 3277 Sources: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a1e3b4bf-22e9-430a-a768-4d86ae886c9e	no
CYP3A 298	inhibitor 3277 Sources: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a1e3b4bf-22e9-430a-a768-4d86ae886c9e	no
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
MRP2 475	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
MRP3 207	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
OATP1B1 803	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
OCT1 543	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
P-gp 1650	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	no
OATP1B1/3 12	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20381614/	yes [Inhibition 10 uM]
OCT1 543	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20381614/	yes [Inhibition 10 uM]
CYP1A2 1692	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16012077/	no
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16012077/	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16012077/	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16012077/	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16012077/	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16012077/	no
CYP3A4 1737	substrate 3367 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
Estazolam treatment of insomnia in generalized anxiety disorder: a placebo-controlled study.	1991 Aug	1918423
Metabolic alkalosis and myoclonus from antacid ingestion.	1996 Jun	8835608
[Two complex suicidal poisonings with drugs and their medicolegal aspects].	2001	11450365
Central serotonergic mechanisms on head twitch response induced by benzodiazepine receptor agonists.	2001	11287817
Utilization of psychotropic drugs in Taiwan: an overview of outpatient sector in 2000.	2002 Aug	12455808
[The application of a broard spectrum automatic rapid drug identification system in acute drug poisoning].	2002 Jun	12137605
Determination of estazolam in plasma by high-performance liquid chromatography with solid-phase extraction.	2002 May	12036118
Antidepressant-related hypomania in a patient with premenstrual dysphoric disorder.	2002 Oct	12352284
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
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
Pharmacokinetics and drug interactions of the sedative hypnotics.	2003 Winter	14561946
Overview of the therapeutic management of insomnia with zolpidem.	2004	15291010
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	15193727
Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds.	2005	16336040
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
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
[Randomized and controlled study on effect of acupuncture on sleep quality in the patient of primary insomnia].	2007 Dec	18271228
Sensitive and selective liquid chromatography-tandem mass spectrometry method for the quantification of aniracetam in human plasma.	2007 Oct 15	17826366
Comparative bioavailability of two estazolam tablet formulations in Indonesian healthy volunteers.	2008	19025059
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	17555899
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
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
[Simultaneous determination of 5 sedative hypnotics in human plasma by reversed phase high-performance liquid chromatography].	2009 Jul	19648689
Forty cases of insomnia treated by suspended moxibustion at Baihui (GV 20).	2009 Jun	19663092
[Effect of modified xiaoyao powder for improving sleep in patients with psychological stress insomnia].	2009 Mar	19548434
[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
Algorithms for the assessment and management of insomnia in primary care.	2009 Nov 3	19936140
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
Four cases of dysthymic disorder and general malaise successfully treated with traditional herbal (kampo) medicines: kamiuntanto.	2010	21614161
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443
[The influence of estazolam on human neurobehavioral function].	2010 Feb	20232740

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 `Fri Dec 15 15:23:27 GMT 2023` Edited by `admin` on `Fri Dec 15 15:23:27 GMT 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