Ivabradine (a hyperpolarization activated cyclic nucleotide-gated channel blocker) elevates the threshold for maximal electroshock-induced tonic seizures in mice.
Journal Title: Pharmacological Reports - Year 2013, Vol 65, Issue 5
Abstract
Background: The aim of this study was to determine the effect of ivabradine (a hyperpolarization activated cyclic nucleotide-gated channel (HCN) blocker) on the threshold for maximal electroshock (MEST)-induced tonic seizures in mice. Methods: Electroconvulsionswere produced inmice by means of a current (sine-wave, 50Hz, maximum 500 V, strength from 3-10 mA, ear-clip electrodes, 0.2-s stimulus duration, tonic hindlimb extension taken as the endpoint). Results: Ivabradine administered intraperitoneally (ip), 60 min before the MEST test, at doses of 5 and 10 mg/kg, did not alter the threshold for maximal electroconvulsions in mice. In contrast, ivabradine at doses of 15 and 20 mg/kg significantly elevated the threshold for maximal electroconvulsions in mice (p < 0.05 and p < 0.001, respectively). Linear regression analysis of ivabradine doses and their corresponding threshold increases allowed determination of the threshold increasing doses by 20 and 50% (TID20 and TID50 values) that elevate the threshold in drug-treated animals over the threshold in control animals. The experimentally derived TID20 and TID50 values for ivabradine were 8.70 and 18.29 mg/kg, respectively. Conclusions: Based on this preclinical study, one can ascertain that ivabradine dose-dependently increased the threshold for MEST-induced seizures, suggesting the antiseizure activity of the compound in this seizure model in mice.
Authors and Affiliations
Jarogniew Łuszczki, Andrzej Prystupa, Marta Andres-Mach, Ewa Marzęda, Magdalena Florek-Łuszczki
Keywords
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