Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Fundam Clin Pharmacol. 2020 Feb;34(1):148-155. doi: 10.1111/fcp.12490. Epub 2019 Jul 1.
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 (K ) 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 K channels. Acute intraperitoneal administration of melatonin (40 and 80 mg/kg) increased clonic seizure threshold induced by intravenous administration of PTZ. Melatonin (40 and 80 mg/kg) increased the latency of clonic seizure and reduced its frequency in mice receiving an intraperitoneal injection of PTZ. Administration of glibenclamide, a K channels blocker, before intravenous injection of PTZ reduced melatonin anticonvulsant effect. Diazoxide and cromakalim, as K 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 K channels.
褪黑素是一种主要由松果体分泌的神经激素。这种分子具有多种药理学特性，包括改善免疫系统、预防癌症、抗衰老和抗氧化作用。先前的研究已经证明了褪黑素的抗惊厥作用。三磷酸腺苷（ATP）敏感性钾（K+）通道被认为是调节癫痫发作的重要靶点。本研究旨在研究褪黑素对戊四氮（PTZ）诱导的小鼠惊厥的抗惊厥作用，重点研究其调节 K+通道的能力。急性腹腔内给予褪黑素（40 和 80mg/kg）可增加静脉注射 PTZ 诱导的阵挛性惊厥阈值。褪黑素（40 和 80mg/kg）可延长接受腹腔内注射 PTZ 的小鼠的阵挛性惊厥潜伏期，并降低其频率。在静脉注射 PTZ 之前给予 K+通道阻断剂格列本脲可降低褪黑素的抗惊厥作用。二氮嗪和克罗卡林作为 K+通道开放剂，增加了褪黑素在 PTZ 癫痫模型中的抗癫痫作用。这些发现表明，褪黑素的抗惊厥作用可能是通过增加 K+通道的开放获得的。
