Prazepam is a benzodiazepine derivative drug developed by Warner-Lambert in the 1960s.[US Patent 3192199 – Process for the production of I-CYCLO- ALKYL derivatives of I,X-BENZODIAZEPINE] It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties.
Indications
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
Drug withdrawal or
rebound effects.
Desmethyldiazepam, an active metabolite, has a very long half-life of 36 to 200 hours, which contributes to the therapeutic effects of prazepam.
Side effects
Side effects of prazepam are less profound than with other
benzodiazepines.
Excessive
drowsiness and with longer-term use,
drug dependence, are the most common side effects of prazepam.
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.
Tolerance, dependence and withdrawal
Drug tolerance and
drug 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.
Drug 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.
Tolerance, dependence and withdrawal problems may be less severe than with other benzodiazepines, such as
diazepam.
It may be because tolerance is slower to develop with prazepam than with other benzodiazepines.
Abrupt or over-rapid discontinuation of prazepam after long-term use, even at low dosage, may result in a protracted withdrawal syndrome.
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.
Contraindications and special caution
Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol or drug-dependent individuals and individuals with
comorbid psychiatric disorders.
Mechanism of action
Prazepam exerts its therapeutic effects primarily via modulating the benzodiazepine receptor which in turn enhances
GABA function in the brain.
Prazepam like other benzodiazepines has
anticonvulsant properties, but its anticonvulsant properties are not as potent as other benzodiazepines when tested in animal studies.
Pharmacokinetics
Prazepam is metabolised into descyclopropylmethylprazepam (also known as desmethyldiazepam) and 3-hydroxyprazepam which is further metabolised into
oxazepam.
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.
Interactions
Prazepam may interact with
cimetidine.
Alcohol in combination with prazepam increases the adverse effects, particularly performance impairing side effects and
drowsiness.
Overdose
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.
Abuse potential
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.
Toxicity
Animal studies have found prazepam taken during pregnancy results in delayed growth and causes reproductive abnormalities.
Trade names
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.
See also
-
Benzodiazepine
-
Benzodiazepine dependence
-
Long-term effects of benzodiazepines
External links
