Oxazepam

Structural formula
	Structural formula without stereochemistry
General
Non-proprietary name	Oxazepam
other names	( RS ) -7-chloro-3-hydroxy-5-phenyl-2,3-dihydro-1 H -1,4-benzodiazepin-2-one ( IUPAC ) ; (3RS) -7-chloro-3-hydroxy-5-phenyl-1,3-dihydro-2 H -1,4-benzodiazepin-2-one ( Pharmacopoeia ) ; (±) -7-Chloro-3-hydroxy-5-phenyl-2,3-dihydro-1 H -1,4-benzodiazepin-2-one; rac -7-chloro-3-hydroxy-5-phenyl-2,3-dihydro-1 H -1,4-benzodiazepin-2-one; Oxazepamum ( Latin ) ;
Molecular formula	C 15 H 11 ClN 2 O 2
Brief description	white to almost white, crystalline powder
External identifiers / databases
EC number	210-076-9
ECHA InfoCard	100.009.161
PubChem	4616
ChemSpider	4455
DrugBank	DB00842
Wikidata	Q412299
Drug information
ATC code	N05 BA04
Drug class	Benzodiazepines , anxiolytics
properties
Molar mass	286.71 g · mol -1
Physical state	firmly
Melting point	205-206 ° C
solubility	Water: 179 mg l −1 (25 ° C); readily soluble in dioxane , sparingly soluble in dichloromethane and ethanol ;
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: 351
	P: 281
Toxicological data	1540 mg kg −1 ( LD 50 , mouse , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Oxazepam is a chemical compound from the group of benzodiazepines , which is used as a drug with anti-anxiety ( anxiolytic ) and relaxing ( sedative ) properties. H. is used as a tranquilizer with a medium-long duration of action . The indications, contraindications, side effects and interactions are the same as for all benzodiazepines. Oxazepam was founded in 1965 by Dr. Karl Thomae GmbH (today Boehringer Ingelheim ) brought onto the market. Even after a short period of use, psychological and physical dependence can occur, see Harmful use of benzodiazepines .

pharmacology

Oxazepam is a pharmacologically active metabolite of diazepam and no longer forms any active metabolites itself. The onset of action is slower with oxazepam than with most other benzodiazepines, so that it is somewhat less suitable for acute situations than z. B. the similar lorazepam . The duration of action is 8 to 12 hours. Oxazepam and lorazepam are not broken down via the cytochrome P450 system (CYP2C19) and therefore do not change their duration of action even with a CYP2C19 mutation (2–5% of the German population). This is a significant advantage of these substances compared to other benzodiazepines. Since the metabolism only takes place via glucuronidation , a significantly longer duration of action is not to be expected even with more advanced liver damage, which is a further advantage. Nevertheless, in the case of liver cirrhosis, therapy under level control is useful.

Use during pregnancy and breastfeeding

The use of benzodiazepines during pregnancy can cause undesirable effects in the unborn child. Oxazepam should therefore only be taken during pregnancy if clearly necessary. Hypotension, hypothermia, hypoactivity, and respiratory depression can occur in the newborn. Withdrawal symptoms can also appear later. In animal experiments there is evidence of behavioral disorders in the offspring of dams to which benzodiazepines have been administered.

Isomerism

Oxazepam contains a stereocenter . Consequently there are two enantiomers , the ( R ) and the ( S ) isomer, which bind to serum albumins significantly differently .

The synthesis of oxazepam produces the racemate . The enantiomers are unstable and racemize rapidly in aqueous solution with ring opening to the tautomeric imino aldehyde , so that the pharmaceutical use of a pure enantiomer is unnecessary.

Extraction and presentation

Oxazepam can be obtained from demoxepam .

Trade names

Adumbran (D, A), Anxiolit (A, CH), Durazepam (D), Praxiten (D, A), Seresta (CH), numerous generics (D)

literature

O. Benkert, H. Hippius: Psychiatric pharmacotherapy . 6th edition, Springer-Verlag, Berlin-Heidelberg-New York 1996, ISBN 3-540-58149-9 .

Individual evidence

↑ ^a ^b European Pharmacopoeia Commission (ed.): EUROPEAN PHARMACOPOE 5TH EDITION . tape 5.0-5.8 , 2006.
↑ ^a ^b ^c Entry on Oxazepam in the ChemIDplus database of the United States National Library of Medicine (NLM)
↑ ^a ^b Oxazepam data sheet from Sigma-Aldrich , accessed on April 16, 2011 ( PDF ).

↑ Psychiatric Drugs Timeline

^ Specialist information of the Swiss Medicines Compendium: Anxiolit, as of April 2006.

↑ FD Boudinot, CA Homon, WJ Jusko and HW Ruelius: Protein binding of oxazepam and its glucuronide conjugates to human albumin , Biochemical Pharmacology 34 (1985) 2115.

↑ Miklós Simonyi, Joseph Gal and Bernhard Testa: Sings: The Code of Clarification , in Miklós Simonyi, Problems and Wonders if Chiral Molecules , Akadémiai Kiadó, Budapest, 1990, pp. 127-136, ISBN 963-05-5881-5 .

↑ Julio Alvarez-Builla, Juan Jose Vaquero, José Barluenga: Modern Heterocyclic Chemistry, 4 Volume Set . John Wiley & Sons, 2011, ISBN 978-3-527-33201-4 , pp. 2184 ( limited preview in Google Book search).

[Ph._Eur._5-1] European Pharmacopoeia Commission (ed.): EUROPEAN PHARMACOPOE 5TH EDITION . tape 5.0-5.8 , 2006.

[ChemIDplus-2] Entry on Oxazepam in the ChemIDplus database of the United States National Library of Medicine (NLM)

[sigma-3] Oxazepam data sheet from Sigma-Aldrich , accessed on April 16, 2011 ( PDF ).

[4] Psychiatric Drugs Timeline

[5] Specialist information of the Swiss Medicines Compendium: Anxiolit, as of April 2006.

[Boudinot-6] FD Boudinot, CA Homon, WJ Jusko and HW Ruelius: Protein binding of oxazepam and its glucuronide conjugates to human albumin , Biochemical Pharmacology 34 (1985) 2115.

[Simonyi-7] Miklós Simonyi, Joseph Gal and Bernhard Testa: Sings: The Code of Clarification , in Miklós Simonyi, Problems and Wonders if Chiral Molecules , Akadémiai Kiadó, Budapest, 1990, pp. 127-136, ISBN 963-05-5881-5 .

[Julio_Alvarez-Builla,_Juan_Jose_Vaquero,_José_Barluenga-8] Julio Alvarez-Builla, Juan Jose Vaquero, José Barluenga: Modern Heterocyclic Chemistry, 4 Volume Set . John Wiley & Sons, 2011, ISBN 978-3-527-33201-4 , pp. 2184 ( limited preview in Google Book search).