Clotiazepam

Structural formula
General
Non-proprietary name	Clotiazepam
other names	5- (2-chlorophenyl) -7-ethyl-1-methyl-3 H -thieno [2,3- e ] [1,4] diazepin-2-one ( IUPAC )
Molecular formula	C 16 H 15 CIN 2 OS
Brief description	white solid
External identifiers / databases
EC number	251-627-3
ECHA InfoCard	100.046.920
PubChem	2811
ChemSpider	2709
DrugBank	DB01559
Wikidata	Q2263999
Drug information
ATC code	N05 BA21
Drug class	Benzodiazepine; Anxiolytic;
properties
Molar mass	318.82 g · mol -1
Physical state	firmly
Melting point	105-106 ° C
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302
	P: 264-301-312
Toxicological data	636 mg kg −1 ( LD 50 , mouse , oral ) ; 440 mg kg −1 ( LD 50 , mouse , ip ) ; 1461 mg kg −1 ( LD 50 , rat , oral ) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Clotiazepam is a benzodiazepine analog from the group of thienodiazepines and, like all of its analogs, has amnestic , anxiolytic , anticonvulsant , hypnotic , sedative and muscle relaxing potential. It is used as an anxiolytic for anxiety disorders and panic attacks . In Japan and France, due to its sedative properties, it is also approved for premedication before surgical procedures.

Clotiazepam was launched on the German market in 1979 by Bayer under the trade name Trecalmo . Today, clotiazepam is no longer used in Germany; the last drug containing clotiazepam , Trecalmo , was taken off the market here in 2001.

Pharmacokinetics

After oral administration of clotiazepam, maximum plasma concentrations are reached within 0.6–1.5 hours. Clotiazepam and its metabolites hydroxyclotiazepam and desmethylclotiazepam have an elimination half-life of 6.5–18 hours. After repeated dosing, clotiazepam has less of a tendency to accumulate than long-acting benzodiazepines. The equivalent dose to 10 mg diazepam is 5 mg clotiazepam.

Side effects

Common side effects are drowsiness and asthenia . There is one report that clotiazepam caused acute hepatitis . Like all anxiolytics from the benzodiazepine class, clotiazepam has a high potential for dependence and abuse.

Trade names

Monopreparations: Trecalmo (D; withdrawn from the market in 2001), Clozan (BE), Rize (JP), Tienor (IT), Vératran (FR)

Individual evidence

↑ ^a ^b ^c ^d Entry on clotiazepam at Toronto Research Chemicals , accessed on March 17, 2019 ( PDF ).
↑ ^a ^b ^c George W. A. Milne (Ed.): Drugs . Definitions and properties. Routledge, 2018, ISBN 978-1-351-78989-9 ( limited preview in Google Book Search).
↑ DE Patent 2107356
↑ Fukuda T., Tsumagari T .: Effects of psychotropic drugs on the rage responses induced by electrical stimulation of the medial hypothalamus in cats. . In: Japanese Journal of Pharmacology 33 . 1983, pp. 885-890. doi : 10.1254 / jjp.33.885 . PMID 6632385 .
↑ Mandrioli R., Mercolini L., Raggi MA .: Benzodiazepine metabolism: an analytical perspective. . In: Current Drug Metabolism 9 . 2008, pp. 827-844. doi : 10.2174 / 138920008786049258 . PMID 18855614 .
↑ Martucci N, Manna V, Agnoli A .: A clinical and neurophysiological evaluation of clotiazepam, a new thienodiazepine derivative. . In: International Clinical Psychopharmacology 2 . 1987, pp. 121-128. PMID 2885366 .
↑ Official Japanese Drug Information Sheet (Kusuri-no-Shiori)
↑ French Guide to Medicines - Clotiazepam (Veratran)
↑ Peter Riederer, Gerd Laux: Neuro-Psychopharmaka . Springer-Verlag, 2013, ISBN 978-3-7091-6674-1 , p. 63 (527 pp., Google.de ): "Data on the sale of synthetic psychotropic drugs on the German market."
↑ Ochs HR, Greenblatt DJ, Knüchel M .: Effect of cirrhosis and renal failure on the kinetics of clotiazepam. . In: European Journal of Clinical Pharmacology 30 . 1986, pp. 89-92. doi : 10.1007 / BF00614202 . PMID 2872061 .
↑ F. Habersetzer, D. Larrey, G. Babany, C. Degott, M. Corbic, D. Pessayre, JP. Benhamou: Clotiazepam-induced acute hepatitis . In: J Hepatol . 9, No. 2, Sep 1989, pp. 256-9. doi : 10.1016 / 0168-8278 (89) 90060-3 . PMID 2572625 .

[TRC-1] Entry on clotiazepam at Toronto Research Chemicals , accessed on March 17, 2019 ( PDF ).

[GoogleBuch-2] George W. A. Milne (Ed.): Drugs . Definitions and properties. Routledge, 2018, ISBN 978-1-351-78989-9 ( limited preview in Google Book Search).

[3] DE Patent 2107356

[4] Fukuda T., Tsumagari T .: Effects of psychotropic drugs on the rage responses induced by electrical stimulation of the medial hypothalamus in cats. . In: Japanese Journal of Pharmacology 33 . 1983, pp. 885-890. doi : 10.1254 / jjp.33.885 . PMID 6632385 .

[5] Mandrioli R., Mercolini L., Raggi MA .: Benzodiazepine metabolism: an analytical perspective. . In: Current Drug Metabolism 9 . 2008, pp. 827-844. doi : 10.2174 / 138920008786049258 . PMID 18855614 .

[6] Martucci N, Manna V, Agnoli A .: A clinical and neurophysiological evaluation of clotiazepam, a new thienodiazepine derivative. . In: International Clinical Psychopharmacology 2 . 1987, pp. 121-128. PMID 2885366 .

[RIZE-7] Official Japanese Drug Information Sheet (Kusuri-no-Shiori)

[VRTN-8] French Guide to Medicines - Clotiazepam (Veratran)

[9] Peter Riederer, Gerd Laux: Neuro-Psychopharmaka . Springer-Verlag, 2013, ISBN 978-3-7091-6674-1 , p. 63 (527 pp., Google.de ): "Data on the sale of synthetic psychotropic drugs on the German market."

[10] Ochs HR, Greenblatt DJ, Knüchel M .: Effect of cirrhosis and renal failure on the kinetics of clotiazepam. . In: European Journal of Clinical Pharmacology 30 . 1986, pp. 89-92. doi : 10.1007 / BF00614202 . PMID 2872061 .

[11] F. Habersetzer, D. Larrey, G. Babany, C. Degott, M. Corbic, D. Pessayre, JP. Benhamou: Clotiazepam-induced acute hepatitis . In: J Hepatol . 9, No. 2, Sep 1989, pp. 256-9. doi : 10.1016 / 0168-8278 (89) 90060-3 . PMID 2572625 .