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To assess the effect of 3 calcium channel antagonists (amlodipine, diltiazem, and verapamil) on the anticonvulsant action of topiramate (a new generation antiepileptic drug) in the mouse maximal electroshock seizure (MES) model. Amlodipine (20 mg/kg) significantly enhanced the anticonvulsant activity of topiramate in the MES test in mice, reducing its ED50 value from 54.83 to 33.10 mg/kg (p < 0.05). Similarly, diltiazem (5 and 10 mg/kg) markedly potentiated the antiseizure action of topiramate against MES, lowering its ED50 value from 54.83 to 32.48 mg/kg (p < 0.05) and 28.68 mg/kg (p < 0.01), respectively. In contrast, lower doses of amlodipine (5 and 10 mg/kg) and diltiazem (2.5 mg/kg) and all doses of verapamil (5, 10, and 20 mg/kg) had no significant impact on the antiseizure action of topiramate. Pharmacokinetic verification of the interaction of topiramate with amlodipine and diltiazem revealed that neither amlodipine nor diltiazem affected total brain topiramate concentration in experimental animals, and thus, the observed interactions were concluded to be pharmacodynamic in nature. The favorable combinations of topiramate with amlodipine or diltiazem deserve more attention from a clinical viewpoint because the enhanced antiseizure action of topiramate was not associated with any pharmacokinetic changes in total brain topiramate concentration.

The aim of this study was to assess the effect of three calcium channel antagonists (amlodipine, diltiazem and verapamil) on the anticonvulsant action of lamotrigine (a second generation antiepileptic drug) against maximal electroshock-induced seizures in mice. Results indicated that all three calcium channel antagonists when administered alone [amlodipine (up to 20 mg/kg, ip), diltiazem (up to 10 mg/kg, ip) and verapamil (up to 20 mg/kg, ip)], did not significantly affect the threshold for maximal electroconvulsions in mice. However, amlodipine at a non-protective dose of 20 mg/kg, ip significantly enhanced the anticonvulsant activity of lamotrigine in the maximal electroshock-induced seizure test in mice by reducing its ED(50) value from 6.33 to 2.87 mg/kg (p < 0.05). In contrast, amlodipine at lower doses of 5 and 10 mg/kg, ip, diltiazem (at doses up to 10 mg/kg, ip) and verapamil (at doses up to 20 mg/kg, ip) had no significant impact on the antiseizure action of lamotrigine in the maximal electroshock-induced seizure test in mice. In conclusion, one can ascertain that the favorable combination of lamotrigine with amlodipine deserves more attention from a clinical viewpoint because of the enhanced antiseizure action of lamotrigine.