title: Ivabradine (a hyperpolarization activated cyclic nucleotide-gated channel blocker) elevates the threshold for maximal electroshock-induced tonic seizures in mice.
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.affiliation: Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, PL 20-950 Lublin, Poland. jarogniew.luszczki@gmail.com, jluszczki@yahoo.com.
authors.forename: Jarogniew J
authors.initials: JJ
authors.lastname: Luszczki
authors.forename: Andrzej
authors.initials: A
authors.lastname: Prystupa
authors.forename: Marta
authors.initials: M
authors.lastname: Andres-Mach
authors.forename: Ewa
authors.initials: E
authors.lastname: Marzęda
authors.forename: Magdalena
authors.initials: M
authors.lastname: Florek-Łuszczki
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D000077550:Ivabradine; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D012640:Seizures / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology
chemical_list: D000927:Anticonvulsants; D001552:Benzazepines; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D000077550:Ivabradine