[A pharmacological profile of clobazam (Mystan), a new antiepileptic drug].
Clobazam (CLB) is a new antiepileptic drug that is the first 1,5-benzodiazepine (BZP) having nitrogen atoms in the 1 and 5 positions of the heterocyclic ring, whose chemical structure was designed to give it a different pharmacological profile from that of 1,4-BZPs. Although CLB has a Ki value of 2,130 nM and thus has a lower affinity for the BZP receptor than 1,4-BZPs, it had the selectivity to omega 2 receptor contributing to anticonvulsive actions compared with omega 1 receptor in relation to other CNS activities such as sedation. CLB had a wide spectrum of anticonvulsive actions against seizures in several animal models induced by chemical convulsants and maximal electroshock. CLB reduced both seizure stage and afterdischarge duration in a dose-dependent manner in amygdala or hippocampal kindled rats. Usefulness of an anticonvulsant is generally assessed by quoting the protective index (PI) in the ratio of TD50 to ED50. As the PI for CLB was greater than that for 1,4-BZPs, it suggested that CLB was superior to 1,4-BZPs in tolerability while showing anticonvulsive actions. In clinical studies, CLB was used as an adjunctive treatment in patients with refractory epilepsies. From both experimental and clinical observations, CLB was proven to possess a wide spectrum of activity, high effectiveness and good tolerability in several types of epilepsies.
Nakajima
H
H
Pharmaceuticals Promotion Dept., Nesco Company, Azwell, Inc., 2-9, Kokumachi 2-chome, Chuo-ku, Osaka 540-8575, Japan. hi-nakajima@azwell.co.jp
D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001569:Benzodiazepines; D002986:Clinical Trials as Topic; D000078306:Clobazam; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy; D006801:Humans; D051381:Rats; D018079:Receptors, GABA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D000078306:Clobazam