Anticonvulsant effect of melatonin through ATP-sensitive channels in mice.

Abstract

Melatonin is a neurohormone secreted principally by the pineal gland. This molecule has various pharmacological properties including improving immune system, prevent cancer, anti-aging, and anti-oxidant effects. The anticonvulsant effects of melatonin have been proved by previous studies. Adenosine triphosphate (ATP)-sensitive potassium (KATP ) channels are considered as an important target in the seizure modulation. The aim of the present study was to investigate the anticonvulsant effect of melatonin in pentylenetetrazole (PTZ)-induced seizures in mice, focusing on its ability to regulate KATP channels. Acute intraperitoneal administration of melatonin (40 and 80mg/kg) increased clonic seizure threshold induced by intravenous administration of PTZ. Melatonin (40 and 80mg/kg) increased the latency of clonic seizure and reduced its frequency in mice receiving an intraperitoneal injection of PTZ. Administration of glibenclamide, a KATP channels blocker, before intravenous injection of PTZ reduced melatonin anticonvulsant effect. Diazoxide and cromakalim, as KATP channels openers, increased antiseizure effect of melatonin in PTZ model of seizures. These findings suggest that the antiseizure effect of melatonin probably is gained through increasing the opening of KATP channels.