Anticonvulsant Profile of Ondansetron in Rats

Recent studies have shown the involvement of 5-hydroxytryptamine (5HT) in the pathogenesis of epilepsy. Hence it was decided to investigate the effect of the 5HT(3) receptor antagonist ondansetron against maximal electroshock (MES)-induced seizures in rats. Also, the anticonvulsant activity of ondansetron in combination with phenytoin and its effect on the cognitive deficits induced by phenytoin were studied. MES was induced through ear-clip electrodes using a current strength of 150 mA for 0.2 second. The index of protection was taken as the inhibition of tonic hindlimb extension. The ED25 and ED16 doses of ondansetron were combined with subanticonvulsant doses of phenytion, i.e., 6 and 3 mg/kg. The retention latencies in the passive avoidance task (PAT) were assessed on Days 1 and 21 of chronic administration of ondansetron alone, phenytoin alone, and ondansetron in combination with phenytoin. The ED50 of ondansetron was found to be 1.05 (0.51-2.2) mg/kg. The combination of ondansetron with phenytoin had a potentiating effect against MES. Also, the retention latencies in the PAT of ondansetron alone and ondansetron in combination with phenytoin were significantly higher than that of phenytoin alone. Thus, ondansetron has potent anticonvulsant activity in rats and further potentiates the anticonvulsant activity of phenytoin. Also, it attenuates the cognitive dysfunction induced by phenytoin and merits further research for its mechanisms. (C) 2000 Academic Press