Anti-seizure efficacy of nimodipine in pentylenetetrazole and kainic acid combined seizure models in mice.

The present study aimed at establishing two models of experimental seizures by combination treatment with subconvulsive doses of PTZ and kainic acid in adult male mice and evaluating the modulatory role of cerebroselective dihydropyridine calcium channel blocker, nimodipine. The CD50 +/- SEM value for PTZ was found to be 20.00 +/- 0.92 mg/kg, ip in kainic acid (administered at per se subconvulsive dose of 1.00 mg/kg, ip) pretreated mice while CD50 +/- SEM value for kainic acid was found to be 0.30 +/- 0.08 mg/kg, ip in PTZ (administered at per se subconvulsive dose of 30.00 mg/kg, ip) pretreated mice. Nimodipine (5.00 mg/kg, ip) significantly protected the mice from seizure in both of the combination in vivo seizure models. The results suggested synergistic interaction between PTZ and kainic acid at subconvulsive dose combination while the protective efficacy of nimodipine suggested the role of calcium ion as an important mediator for the genesis of seizures.

Pentylenetetrazol-induced kindling in animals: protective effect of BR-16A.

Repeated administration of pentylenetetrazol (PTZ, 30 mg/kg, thrice a week) to mice for 9 weeks and subsequent challenge of the animals with the same dose of PTZ on the last chronic dose produced chemical kindling. The mice showed myoclonic jerks, clonus, Straub's tail, falling back response and full blown convulsions. The anticonvulsant profile of chronic administration of BR-16A (100 and 500 mg/kg) was studied in this model of epilepsy. BR-16A offered protection against PTZ-induced chemical kindling. The per cent animals showing myoclonic jerks and clonus was reduced to 40 and 34 with 100 mg/kg and 54 and 27 with 500 mg/kg of BR-16A, respectively. The protective effect was compared with diazepam (1 mg/kg, ip). The results demonstrated GABAA receptor mediated PTZ-induced kindling and protective effect of BR-16A therein.