Effect of amlodipine on the antiepileptic action of lamotrigine, gabapentin and topiramate on maximal electroshock induced seizures in mice

Abstract

Background: The development of newer classes of antiepileptic drugs has created several opportunities for the treatment of epilepsy. Aims & Objective: The present study was designed to assess the$effect of amlodipine on the antiepileptic action of lamotrigine, gabapentin and topiramate in the mouse maximal electroshock-induced seizure model. Materials and Methods: 300 Adult male mice were divided into 8 groups: (1) control to determine CS50; (2) amlodipine at doses of 5 mg/kg, 10 mg/kg and 20 mg/kg; (3) to determine ED50 of lamotrigine alone; (4) to determine ED50 of lamotrigine after amlodipine; (5) to determine ED50 of gabapentin alone; (6) to determine ED50 of gabapentin after amlodipine; (7) to determine ED50 of topiramate alone; (8) to determine ED50 of topiramate after amlodipine. Results: It was found that amlodipine (up to 20 mg/kg), did not affect the electroconvulsive threshold in mice thus, it has no anticonvulsant effect. Moreover, amlodipine at doses of 10 and 20 mg/kg significantly enhanced the antiseizure action of the three anti convulsant drugs. Amlodipine through the blockade of N- and P/Q type calcium channels enhances the effects of lamotrigine related to the reduction of glutamate release from neurons. It binds to the alpha2 sigma subunit of voltage gated calcium channels, this may explain the observed interaction between gabapentin and amlodipine in the maximal electroshock-induced seizures in mice. Topiramate inhibits voltage-dependent sodium and L-type calcium channels. Its effect on calcium channels may explain the interaction with amlodipine. Conclusion: Amlodipine potentiates the anticonvulsant action of lamotrigine, gabapentin and topiramate.