Effects of amlodipine, diltiazem, and verapamil on the anticonvulsant action of topiramate against maximal electroshock-induced seizures in mice

Canadian Journal of Physiology and Pharmacology
Jarogniew J LuszczkiStanisław J Czuczwar

Abstract

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 ...Continue Reading

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Jun 21, 2011·Journal of Pharmacy & Bioallied Sciences·Anamika ThakurJ S Thakur
Jun 21, 2014·Pharmacological Reports : PR·Kinga K Borowicz, Monika Banach
Sep 22, 2009·Canadian Journal of Physiology and Pharmacology·Mirza Irfan BeigAnju Katyal
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Mar 11, 2017·Metabolic Brain Disease·Itefaq Hussain QureshiAfaq Ahmed Siddiqui
Jul 8, 2019·Epilepsy & Behavior : E&B·Gaetano Zaccara, Simona Lattanzi
Dec 12, 2020·Expert Review of Clinical Pharmacology·Kinga K Borowicz-ReuttMarta Rusek

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