RESUMEN
The present study aimed at establishing the CD50 and CD99 doses along with complete dose-response profile of two convulsants, namely, kainic acid and pentylenetetrazole (PTZ), in mice and evaluating the modulatory role of the cerebroselective dihydropyridine calcium channel blocker nimodipine. Kainic acid and PTZ were administered intraperitoneally in a dose range of 1-30 mg kg(-1) and 35-75 mg kg(-1), respectively. Nimodipine was administered in graded doses (1-8 mg kg(-1), i.p.) with 15 min pretreatment time against CD99 doses of both kainic acid and PTZ. The effect of nimodipine in treated groups was compared with that of vehicle in control group. The CD50 and CD99 doses for kainic acid was found to be 2.5 and 7.5 mg kg(-1), while those of PTZ were found to be 50 and 75 mg kg(-1), respectively. Pretreatment with nimodipine inhibited seizures in a dose-dependent manner, in terms of both percentage of positive responders and seizure scores against CD99 doses of both kainic acid and PTZ. The results established the protective efficacy of nimodipine against both kainic acid and PTZ-induced seizures, suggesting the role of calcium ion as a common mediator for both the types of seizures. However, further studies are necessary to ascertain the exact molecular mechanism of nimodipine.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Convulsivantes/toxicidad , Nimodipina/farmacología , Convulsiones/prevención & control , Animales , Calcio/metabolismo , Relación Dosis-Respuesta a Droga , Ácido Kaínico/toxicidad , Masculino , Ratones , Pentilenotetrazol/toxicidad , Convulsiones/inducido químicamenteRESUMEN
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.