Effects of some convulsant agents on the protective activity of topiramate against maximal electroshock-induced seizures in mice.

The anticonvulsant activity of topiramate combined with some convulsant agents (bicuculline--BIC, N-methyl-D-aspartate--NMDA, and kainic acid--KA), given at subconvulsive doses, was evaluated in the maximal electroshock (MES)-test in mice. BIC (1.5 mg/kg), KA (10 mg/kg) and NMDA (50 mg/kg) significantly decreased the anticonvulsant activity of topiramate raising its ED(50) from 76.2 mg/kg to 135, 102, and 107 mg/kg, respectively. BIC (0.75 mg/kg) and KA (5 mg/kg) did not alter the protective activity of topiramate in the MES-test. Moreover, topiramate injected alone (up to 135 mg/kg) did not affect motor performance and long-term memory of animals tested in the chimney and passive avoidance tests, respectively. In contrast, combinations of topiramate with BIC (1.5 mg/kg), NMDA (50 mg/kg) or KA (10 mg/kg) considerably disturbed long-term memory in mice. Additionally, co-administration of topiramate with KA (10 mg/kg) or BIC (1.5 mg/kg) significantly impaired motor performance, whereas topiramate co-administered with NMDA (50 mg/kg) had no impact on motor coordination in mice. None of the studied convulsants affected the free plasma concentration of topiramate assayed with immunofluorescence method. The results of this study seem to indicate the expression of the anticonvulsant activity of topiramate is dependent on all ionotropic glutamate and GABAA receptor-mediated events.

Influence of LY 300164 alone or in combination with carbamazepine or diphenylhydantoin on the body temperature in mice.

This study was aimed at evaluating the body temperature of mice following the injection of LY 300164, an AMPA/kainate receptor antagonist, alone or in combination with carbamazepine or diphenylhydantoin. LY 300164, injected alone at the dose of 2 mg/kg, produced a potent hypothermic effect between 15 and 30 min, or 60 and 90 min, after the drug administration. The combined treatment of LY 300164 (2 mg/kg) with diphenylhydantoin (3.6 mg/kg) resulted in a significant decrease of body temperature at the time period between 0 and 30 min, whilst LY 300164 (2 mg/kg) co-administered with carbamazepine (5 mg/kg) did not affect the animal temperature. Moreover, either diphenylhydantoin (11.8 mg/kg) or carbamazepine (15.8 mg/kg) injected alone exerted the hypothermic effects elicited at times ranging between 0 and 15 min, or 60 and 90 min, after the respective drug dose administration. In conclusion, hypothermia induced by LY 300164 along with its neuroprotective effects, may be useful in various brain conditions related with neuronal loss in which hypothermia offers some profitable effects, prolonging a survival rate of neurons in the central nervous system.