Ivabradine (a hyperpolarization activated cyclic nucleotide-gated channel blocker) elevates the threshold for maximal electroshock-induced tonic seizures in mice. 2013

Jarogniew J Luszczki, and Andrzej Prystupa, and Marta Andres-Mach, and Ewa Marzęda, and Magdalena Florek-Łuszczki
Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, PL 20-950 Lublin, Poland. jarogniew.luszczki@gmail.com, jluszczki@yahoo.com.

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.

UI MeSH Term Description Entries
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D008297 Male Males
D008568 Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory.
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004597 Electroshock Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. Electroconvulsive Shock,Electroconvulsive Shocks,Electroshocks,Shock, Electroconvulsive,Shocks, Electroconvulsive
D000077550 Ivabradine A benzazepine derivative and selective HYPERPOLARIZATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED CHANNELS inhibitor that lowers the heart rate. It is used in the treatment of CHRONIC STABLE ANGINA in patients unable to take BETA-ADRENERGIC BLOCKERS, and in the treatment of HEART FAILURE. 7,8-Dimethoxy-3-(3-(((4,5-dimethoxybenzocyclobutan-1-yl)methyl)methylamino)propyl)-1,3,4,5-tetrahydro-2H-benzazepin-2-one,Corlanor,S 16257,S 16257-2,S 16260-2,S-16257,S-16257-2,S-16260-2,S 16257 2,S 162572,S 16260 2,S 162602,S16257,S162572,S162602
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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