Verapamil enhances the anticonvulsant effect of oxcarbazepine in the maximal electroshock-induced seizure model in mice

The aim of this study was to assess the influence of verapamil (an L-type calcium channel blocker) on the anticonvulsant potential of oxcarbazepine (a second-generation antiepileptic drug) in the maximal electroshock seizure (MES) test in mice. Electroconvulsions were evoked in Albino Swiss mice by a current (25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Adverse-effect profiles with respect to motor coordination, long-term memory and skeletal muscular strength were measured along with total brain oxcarbazepine concentrations. Verapamil (20 mg/kg, i.p.) significantly enhanced the anticonvulsant activity of oxcarbazepine in the MES test in mice, by reducing its ED50 value from 12.24 to 7.48 mg/kg (P<0.01). In contrast, verapamil (5 and 10 mg/kg) had no significant impact on the antiseizure action of oxcarbazepine in the MES test in mice. Moreover, verapamil (20 mg/kg) significantly elevated total brain oxcarbazepine concentrations in mice as measured with high-pressure liquid chromatography. The combination of oxcarbazepine with verapamil, at doses from the MES test, did not impair motor coordination in the chimney test, long- term memory in the passive avoidance task, or skeletal muscular strength in the grip-strength test in mice. In conclusion, the utmost caution is advised when combining oxcarbazepine with verapamil due to a possible pharmacokinetic increase in total brain oxcarbazepine concentrations in patients receiving both drugs.