Ivabradine (a hyperpolarization activated cyclic nucleotide-gated channel blocker) elevates the threshold for maximal electroshock-induced tonic seizures in mice

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 bymeans of a current (sine-wave,50hz,maximum500v,strength from3-10ma,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. copyright © 2013 by institute of pharmacology polish academy of sciences.