Clobazam anticonvulsant

Benzodiazepines are the drugs of choice for status epilepticus (see above) however, development of tolerance renders them less suitable for long-term therapy. Clonazepam is used for myoclonic and atonic seizures. Clobazam, a 1,5-benzodiazepine exhibiting an increased anticonvulsant/seda-tive activity ratio, has a similar range of clinical uses. Personality changes and paradoxical excitement are potential side effects. 

Clonazepam is the most potent of the benzodiazepine anticonvulsants and is particularly indicated in the treatment of the more difficult cases of epilepsy, especially those of the multiple seizure type. More recently, clobazam, which at therapeutic doses has the advantage of causing little... 

Clobazam, a 1,5-benzodiazepine, differs in its chemical structure from most other benzodiazepines. It has been claimed to have less sedative effects for its effective anticonvulsant and anti-anxiety effects (SED-12, 98). Whether because of tolerance or not, clobazam tends to be less sedative than clonazepam. Both the therapeutic and adverse effects of clobazam have been related to its major metabolite Al-desmethylclobazam, the formation of which depends on CYP2C19 activity. Mutant alleles that confer high CYP2C19 activity, and are therefore associated with high concentrations of the metabolite, are particularly common (30-40%) in Asian populations (1)-... 

Clobazam has similar effects on anxiety to other benzodiazepines, but may be better tolerated (SEDA-20, 31). Used as an anticonvulsant, clobazam is generally well tolerated in epileptic patients, many showing little evidence of tolerance (5). On the other hand, children with epilepsy appear unusually prone to adverse behavioral reactions when taking clobazam (SEDA-19, 34). 

Valproate, clonazepam, or clobazam may be safer alternatives in patients who have had a rash from aromatic anticonvulsants. However, in a 41-year-old man a fixed drug eruption that occurred after phenytoin and carbamazepine also occurred after valproate (SEDA-22, 83). 

Clobazam and Nitrazepam. Two new investigational benzodiazepines appear to be safe and effective as anticonvulsants. However, these agents have long elimination half-lives that increase the potential not only for drug accumulation but also for residual side effects. 

Clobazam. Clobazam (4d) differs from the previous benzodiazepines, given that it is a 1,5-benzodiazepine rather than a 1,4-derivative. It was demonstrated that N-desmethyl-clobazam (4k) possessed anticonvulsant activity (50,51). 

A review of the second-generation anticonvulsants reveals that screening or serendipity led to the development of felbamate (10), 1am-otrigine (11), zonisamide (13), topiramate (15), and levetiracetam (16) on the other hand, clobazam (4d) and oxcarbazepine (12) were developed by structural variation of known agents (78). Only three, vigabatrin (8), gabapentin (9), and tiagabine (14), were developed by mechanism-based rational development (78). 

Anticonvulsants - Clobazam (.2 ) blocked convulsive seizures in mice and baboons.The 7-bromobenzodlazepine Jn was the best of a series In protection against PTZ and maximal electroshock (MES)-lnduced convulsions in mice. 

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