Clorazepate
Clinical data | |
---|---|
Trade names | Tranxene, Tranxilium, Novo-Clopate |
Other names | Clorazepate dipotassium |
AHFS/Drugs.com | Monograph |
MedlinePlus | a682052 |
Routes of administration | Oral |
ATC code | |
Legal status | |
Legal status |
|
Renal | |
Identifiers | |
| |
JSmol) | |
| |
| |
(what is this?) (verify) |
Clorazepate, sold under the brand name Tranxene among others, is a
It was patented in 1965 and approved for medical use in 1967.[3]
Medical uses
Clorazepate is used in the treatment of anxiety disorders and insomnia. It may also be prescribed as an anticonvulsant or muscle relaxant.[4] It is also used as a premedication.[5]
Clorazepate is prescribed principally in the treatment of
Adverse effects
Adverse effects of clorazepate include
In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of non-medical use, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.[8]
Tolerance, dependence and withdrawal
Delirium has been noted from discontinuation from clorazepate.[9] A
Interactions
All
Contraindications and special caution
Benzodiazepines require special precaution if used in the elderly, children, alcohol- or drug-dependent individuals and individuals with
Clorazepate if used late in pregnancy, the
Special precaution is required when using clorazepate in the elderly because the elderly metabolise clorazepate more slowly, which may result in excessive drug accumulation. Additionally the elderly are more sensitive to the adverse effects of benzodiazepines compared to younger individuals even when blood plasma levels are the same. Use of benzodiazepines in the elderly is only recommended for 2 weeks and it is also recommended that half of the usual daily dose is prescribed.[7]
Pharmacology
Clorazepate is a "classical" benzodiazepine. Other classical benzodiazepines include
Chemistry
Clorazepate is used in the form of a dipotassium salt. It is unusual among benzodiazepines in that it is freely soluble in water.
Clorazepate can be synthesized starting from 2-amino-5-chlorobenzonitrile, which upon reaction with phenylmagnesium bromide is transformed into 2-amino-5-chlorbenzophenone imine.[14][15][16] Reacting this with aminomalonic ester gives a heterocyclization product, 7-chloro-1,3-dihydro-3-carbethoxy-5-phenyl-2H-benzodiazepin-2-one. Upon hydrolysis using an alcoholic solution of potassium hydroxide forms a dipotassium salt, chlorazepate.
Legal status
In the United States, clorazepate is listed under Schedule IV of the Controlled Substances Act.[17]
References
- ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
- S2CID 24414335. Archived from the originalon 2009-07-20. Retrieved 2009-05-31.
- ISBN 9783527607495.
- ^ a b National Institutes of Health (2003). "Clorazepate". National Library of Medicine. Archived from the original on 20 May 2008. Retrieved 19 July 2008.
- PMID 17551699.
- ^ Tranxene prescribing information in the Netherlands (Dutch language); accessed 2007-03-08.
- ^ ]
- ^ "FDA expands Boxed Warning to improve safe use of benzodiazepine drug". U.S. Food and Drug Administration (FDA). 23 September 2020. Retrieved 23 September 2020. This article incorporates text from this source, which is in the public domain.
- PMID 27202.
- ^ PMID 7388368.
- PMID 19900604.
- PMID 7881198.
- PMID 639854.
- ^ US 3516988, Schmitt J, "1,4 benzodiazepine-2-ones having a carboxylic acid ester or amide group in the 3-position", issued 23 June 1970
- ^ DE 1518764, Schmitt J, "Verfahren zur Herstellung von Orthoaminoarylcetiminen [Process for the preparation of orthoaminoarylcetimins]", published 1971-11-04, assigned to Etablissements Clin-Byla S.A.
- ^ Schmitt J, Comoy P, Suguet M, Calief G, Muer J, Clim T, et al. (1969). "Sur des nouvelles benzodiazepines hydrosolubles douées d'une puissante activité sur le système nerveux central" [On new water-soluble benzodiazepines endowed with a powerful activity on the central nervous system.]. Chim. Ther. (in French). 4: 239.
- ^ "List of Schedule 4 (IV) Controlled Substances". Drugs.com. Retrieved 27 March 2024.