CLOTIAZEPAM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H15ClN2OS
Molecular Weight	318.821
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC1=CC2=C(S1)N(C)C(=O)CN=C2C3=CC=CC=C3Cl

InChI

InChIKey=CHBRHODLKOZEPZ-UHFFFAOYSA-N

InChI=1S/C16H15ClN2OS/c1-3-10-8-12-15(11-6-4-5-7-13(11)17)18-9-14(20)19(2)16(12)21-10/h4-8H,3,9H2,1-2H3

HIDE SMILES / InChI

Description
Sources: https://www.aemps.gob.es/cima/pdfs/es/p/55479/55479_p.pdf | https://www.ncbi.nlm.nih.gov/pubmed/18604239

Clotiazepam is a compound of the benzodiazepine class. The drug was developed in Japan and approved for the treatment of insomnia, anxiety and before anesthesia. Clotiazepam was marketed worlwide under different names, however, currently it is available only in South America under the name Neuroval and presumably in Japan. Clotiazepam exerts its action by binding and activating GABA-A receptors.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; benzodiazepine site 38 Target ID: CHEMBL2109243 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18604239	Agonist 2752		184.0 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Insomnia 111 Sources: https://www.aemps.gob.es/cima/pdfs/es/p/55479/55479_p.pdf	Primary	Approved 8583	DISTENSAN Approved Use Doctors prescribe Distensan for disorders in the sleep rhythm and all forms of insomnia, especially when there are difficulties in falling asleep, either initially or after premature awakening. In most cases only a short-term treatment with Distensan (usually not more than two weeks) is needed. Distensan is also used for the treatment of anxiety, nervous tension, irritability emotional disturbances and before anesthesia (anesthetic premedication).
Anxiety 275 Sources: https://www.aemps.gob.es/cima/pdfs/es/p/55479/55479_p.pdf	Primary	Approved 8583	NEUROVAL Approved Use The treatment of anxiety.
Pain 619 Sources: https://www.aemps.gob.es/cima/pdfs/es/p/55479/55479_p.pdf	Preventing	Approved 8583	DISTENSAN Approved Use Doctors prescribe Distensan for disorders in the sleep rhythm and all forms of insomnia, especially when there are difficulties in falling asleep, either initially or after premature awakening. In most cases only a short-term treatment with Distensan (usually not more than two weeks) is needed. Distensan is also used for the treatment of anxiety, nervous tension, irritability emotional disturbances and before anesthesia (anesthetic premedication).

C_max

Value	Dose	Analyte	Population
178.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2575522/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	CLOTIAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
383 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/300119_1179012F1169_1_071_1F.pdf#page=21	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	CLOTIAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
162 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/300119_1179012F1169_1_071_1F.pdf#page=22	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	CLOTIAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
528.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2575522/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	CLOTIAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1798 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/300119_1179012F1169_1_071_1F.pdf#page=21	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	CLOTIAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
494 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/300119_1179012F1169_1_071_1F.pdf#page=22	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	CLOTIAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
4.62 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2575522/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	CLOTIAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5.3 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/300119_1179012F1169_1_071_1F.pdf#page=21	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	CLOTIAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.4 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/300119_1179012F1169_1_071_1F.pdf#page=22	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	CLOTIAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/300119_1179012F1169_1_071_1F.pdf#page=24 \| https://pubmed.ncbi.nlm.nih.gov/6125154/			CLOTIAZEPAM plasma	Homo sapiens

Doses

Dose	Population	Adverse events
100 mg 1 times / day multiple, oral Highest studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7957524/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7957524/	Disc. AE: Drowsiness, Drowsiness... AEs leading to discontinuation/dose reduction: Drowsiness (grade 3, 6.7%) Drowsiness (grade 3, 6.7%) Gait disturbance (grade 3, 6.7%) Dysarthria (grade 3, 6.7%) Gait disturbance (grade 3, 6.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/7957524/

AEs

AE	Significance	Dose	Population
Drowsiness	grade 3, 6.7% Disc. AE	100 mg 1 times / day multiple, oral Highest studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7957524/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7957524/
Drowsiness	grade 3, 6.7% Disc. AE	100 mg 1 times / day multiple, oral Highest studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7957524/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7957524/
Dysarthria	grade 3, 6.7% Disc. AE	100 mg 1 times / day multiple, oral Highest studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7957524/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7957524/
Gait disturbance	grade 3, 6.7% Disc. AE	100 mg 1 times / day multiple, oral Highest studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7957524/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7957524/
Gait disturbance	grade 3, 6.7% Disc. AE	100 mg 1 times / day multiple, oral Highest studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7957524/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7957524/

PubMed

Title	Date	PubMed
Clocapramine-related fatality. Postmortem drug levels in multiple psychoactive drug poisoning.	2001 Oct 15	11587865
Anoxybacillus ayderensis sp. nov. and Anoxybacillus kestanbolensis sp. nov.	2004 Sep	15388701
Diagnostic performance of Triage for benzodiazepines: urine analysis of the dose of therapeutic cases.	2005 Sep	16168176
Localization of telomeres and telomere-associated proteins in telomerase-negative Saccharomyces cerevisiae.	2007	18075778
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443
Assessing the autoantibody levels in relation to disease severity and therapy response in pemphigus patients.	2010 Oct	21430886

Patents

Sample Use Guides

In Vivo Use Guide

Treatment of anxiety: the usual dose in adults is 1 tablet (10 mg) 1 to 3 times a day for 8-12 weeks. Treatment of insomnia: the usual adult dose is 1 tablet (10 mg) to 2 tablets (20 mg) administered at night, before bedtime. The duration of treatment is usually 2-4 weeks.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

RIZE

Preferred Name

English

CLOTIAZEPAM

Official Name

English

CLOTIAZEPAM [MI]

Common Name

English

CLOTIAZEPAM [MART.]

Common Name

English

Clotiazepam [WHO-DD]

Common Name

English

5-(O-CHLOROPHENYL)-7-ETHYL-1,3-DIHYDRO-1-METHYL-2H-THIENO(2,3-E)-1,4-DIAZEPIN-2-ONE

Common Name

English

CLOTIAZEPAM [JAN]

Common Name

English

clotiazepam [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1012