Prazepam
Prazepam
Benzodiazepine drug
Prazepam is a benzodiazepine derivative drug developed by Warner-Lambert in the 1960s.[2] It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties.[3] Prazepam is a prodrug for desmethyldiazepam which is responsible for the therapeutic effects of prazepam.[4]
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Other names | 9-chloro-2-(cyclopropylmethyl)-6-phenyl-2,5-diazabicyclo[5.4.0]undeca-5,8,10,12-tetraen- 3-one |
AHFS/Drugs.com | Micromedex Detailed Consumer Information |
MedlinePlus | a601036 |
Routes of administration | Oral |
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Metabolism | Hepatic |
Elimination half-life | 36–200 hours |
Excretion | Renal |
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ECHA InfoCard | 100.019.069 |
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Formula | C19H17ClN2O |
Molar mass | 324.81 g·mol−1 |
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Prazepam is indicated for the short-term treatment of anxiety. After short-term therapy, the dose is usually gradually tapered-off to reduce or avoid any withdrawal or rebound effects.[5][6] Desmethyldiazepam, an active metabolite, has a very long half-life of 29 to 224 hours, which contributes to the therapeutic effects of prazepam.[7][8]
Side effects of prazepam are less profound than with other benzodiazepines.[9] Excessive drowsiness and with longer-term use, drug dependence, are the most common side effects of prazepam.[10][11] Side effects such as fatigue or "feeling spacey" can also occur but less commonly than with other benzodiazepines. Other side effects include feebleness, clumsiness or lethargy, clouded thinking and mental slowness.[12][13][14]
Tolerance and dependence can develop with long-term use of prazepam, and upon cessation or reduction in dosage, then a benzodiazepine withdrawal syndrome may occur with symptoms such as tremulousness, dysphoria, psychomotor agitation, tachycardia and sweating. In severe cases, hallucinations, psychosis and seizures can occur. Withdrawal-related psychosis is generally unresponsive to antipsychotic mediations. The risk and severity of the withdrawal syndrome increases the higher the dose and the longer prazepam is taken for.[15] Tolerance, dependence and withdrawal problems may be less severe than with other benzodiazepines, such as diazepam.[16] It may be because tolerance is slower to develop with prazepam than with other benzodiazepines.[17] Abrupt or over-rapid discontinuation of prazepam after long-term use, even at low dosage, may result in a protracted withdrawal syndrome.[18]
Benzodiazepines can induce serious problems of addiction, which is one of the main reasons for their use being restricted to short-term use. A survey in Senegal found that the majority of doctors believed that their training in this area was generally poor. It was recommended that national authorities take urgent action regarding the rational use of benzodiazepines. Almost one-fifth of doctors ignored prescription guidelines regarding short-term use of benzodiazepines, and almost three-quarters of doctors regarded their training and knowledge of benzodiazepines to be inadequate. More training regarding benzodiazepines has been recommended for doctors.[19][20]
Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol or drug-dependent individuals and individuals with comorbid psychiatric disorders.[21]
Prazepam exerts its therapeutic effects primarily via modulating the benzodiazepine receptor which in turn enhances GABA function in the brain.[22] Prazepam like other benzodiazepines has anticonvulsant properties, but its anticonvulsant properties are not as potent as other benzodiazepines when tested in animal studies.[23][24][25][26]
Prazepam is metabolised into descyclopropylmethylprazepam (also known as desmethyldiazepam) and 3-hydroxyprazepam which is further metabolised into oxazepam.[27][28][29][30][31] Prazepam is a prodrug for descyclopropylmethylprazepam/desmethyldiazepam (also known as norprazepam or nordazepam) which is responsible for most of the therapeutic activity of prazepam rather than prazepam itself.[15][22][32][33]
Prazepam may interact with cimetidine.[34] Alcohol in combination with prazepam increases the adverse effects, particularly performance impairing side effects and drowsiness.[35]
The symptoms of an overdose of prazepam include sleepiness, agitation and ataxia. Hypotonia may also occur in severe cases. Overdoses in children typically result in more severe symptoms of overdose.[36]
Prazepam like other benzodiazepines has abuse potential and can be habit forming. However, its abuse potential may be lower than other benzodiazepines because it has a slow onset of action.[15][37]
Animal studies have found prazepam taken during pregnancy results in delayed growth and causes reproductive abnormalities.[38][39][40]
Common trade names include Centrac, Centrax, Demetrin, Lysanxia, Mono Demetrin, Pozapam, Prasepine, Prazene, Reapam and Trepidan. Trade names vary depending on the country; Austria: Demetrin, Belgium: Lysanxia, France: Lysanxia, Germany: Demetrin; Mono Demetrin, Greece: Centrac, Ireland: Centrax, Italy: Prazene; Trepidan, Macedonia: Demetrin, Prazepam, Netherlands: Reapam, Portugal: Demetrin, South Africa: Demetrin, Switzerland: Demetrin, Thailand: Pozapam; Prasepine.[41]
- 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.
- US Patent 3192199 – Process for the production of I-CYCLO- ALKYL derivatives of I,X-BENZODIAZEPINE
- Shader RI, Greenblatt DJ (1979). "Benzodiazepines: some aspects of their clinical pharmacology". Ciba Foundation Symposium. Novartis Foundation Symposia. 1979 (74): 141–155. doi:10.1002/9780470720578.ch9. ISBN 9780470720578. PMID 45081.
- Jacqmin P, Ansseau M (1988). "Comparison of sublingual and oral prazepam in normal subjects. II. Pharmacokinetic and pharmacodynamic data". Neuropsychobiology. 19 (4): 186–191. doi:10.1159/000118458. PMID 2854609.
- Rickels K, Sablosky L, Silverman H, Case WG, Rial W, Mirman M, Gottlieb S (1977). "Prazepam in anxiety: a controlled clinical trial". Comprehensive Psychiatry. 18 (3): 239–249. doi:10.1016/0010-440X(77)90018-9. PMID 858240.
- Danion JM, Brion S, Escande M, Ropert R, Sacquepee L, Singer L, Scotto JC (1984). "[Treatment of anxiety with prazepam, 40 mg. A controlled study versus lorazepam]" [Treatment of anxiety with prazepam, 40 mg. A controlled study versus lorazepam]. L'Encephale (in French). 10 (3): 135–138. PMID 6389091.
- Dièye AM, Sy B, Diarra M, Faye B (March 2004). "[Prescription and use of benzodiazepins in Saint-Louis in Senegal: patient survey]" [Prescription and use of benzodiazepins in Saint-Louis in Senegal: patient survey]. Annales Pharmaceutiques Françaises (in French). 62 (2): 133–137. doi:10.1016/S0003-4509(04)94292-7. PMID 15107731.
- Ansseau M, von Frenckell R, Jacqmin P (1987). "Comparison of sublingual and oral prazepam in normal subjects. I. Clinical data". Neuropsychobiology. 18 (2): 77–82. doi:10.1159/000118397. hdl:2268/249065. PMID 3330182.
- Shader RI, Greenblatt DJ (1981). "The use of benzodiazepines in clinical practice". British Journal of Clinical Pharmacology. 11. 11 (Suppl 1): 5S–9S. doi:10.1111/j.1365-2125.1981.tb01832.x. PMC 1401641. PMID 6133535.
- Saletu M, Saletu B, Grünberger J, Mader R, Karobath M (1983). "Clinical symptomatology and computer analyzed EEG before, during and after anxiolytic therapy of alcohol withdrawal patients". Neuropsychobiology. 9 (2–3): 119–134. doi:10.1159/000117949. PMID 6353268.
- Soyka M, Lehle R, Hippius H (September 1994). "[Exacerbation of an affective psychosis after terminating a decade of benzodiazepine treatment. Which therapeutic procedure is sensible?]" [Exacerbation of an affective psychosis after terminating a decade of benzodiazepine treatment. Which therapeutic procedure is sensible?]. Der Nervenarzt (in German). 65 (9): 628–632. PMID 7991010.
- Dièye AM, Sylla M, Ndiaye A, Ndiaye M, Sy GY, Faye B (June 2006). "Benzodiazepines prescription in Dakar: a study about prescribing habits and knowledge in general practitioners, neurologists and psychiatrists". Fundamental & Clinical Pharmacology. 20 (3): 235–238. doi:10.1111/j.1472-8206.2006.00400.x. PMID 16671957. S2CID 20619323.
- Dièye AM, Sy AN, Sy GY, Diallo AA, Diarra M, Ndiaye M, Faye B (2007). "Prescription des benzodiazépines par les médecins généralistes du privé à Dakar : Enquête sur les connaissances et les attitudes" [Prescription of benzodiazepines by general practitioners in the private sector of Dakar: survey on knowledge and attitudes]. Therapie (in French). 62 (2): 163–168. doi:10.2515/therapie:2007018. PMID 17582318.
- Authier N, Balayssac D, Sautereau M, Zangarelli A, Courty P, Somogyi AA, et al. (November 2009). "Benzodiazepine dependence: focus on withdrawal syndrome". Annales Pharmaceutiques Françaises. 67 (6): 408–413. doi:10.1016/j.pharma.2009.07.001. PMID 19900604.
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