Anticonvulsant activity of melatonin against seizures induced by quinolinate, kainate, glutamate, NMDA, and pentylenetetrazole in mice

Abstract

Melatonin was tested in an ongoing attempt to find the endogenous antagonists of quinolinic acid, an endogenous convulsant. Among a great number of metabolites that have been tried before, only a few were found (cerulein and quinaldic acid in mice and kynurenic acid in rats). In SHR (bred from Swiss) male mice, intracerebroventricular (i.c.v.) pretreatment with melatonin (1.25-10.0 microg) attenuated (in the descending order of potency) the convulsant effect of i.c.v. administered kainate, quinolinate, glutamate, N-methyl-D-aspartate, and pentylenetetrazole. Melatonin was ineffective against i.p. administered pentylenetetrazole. Systemically (intraperitoneal, i.p.) administered melatonin (12.5-100.0 mg/kg) attenuated the convulsant effect of quinolinate, while the action of other convulsants used remained unaltered. It is suggested that melatonin could be tried against grand mal seizures in epileptic patients.

Melatonin, mitochondria, and cellular bioenergetics

“…Both experimental and clinical anticonvulsant activity of melatonin was reported [Molina-Carballo et al, 1997;Lapin et al, 1998]. Reduced melatonin levels are related to increased brain damage after stroke or excitotoxic seizures in rats [Manev et al, 1996], whereas melatonin protected the brain against kainic acid or quinolinic acid oxidative damage Tan et al, 1998;Cabrera et al, 2000].…”

Melatonin Does Not Provide Protection Against Hyperbaric Oxygen (HBO) Induced Seizures

“…The difference between onset time of a seizure and the time at which the rat (17). Given that we observed no differences in seizure latency between the control and DMSO+saline conditions in Experiment 1, we only used DMSO+saline as the control in Experiment 2.…”

“…The occurrence of iron-induced epileptic EEG discharges was reduced in rats given intraperitoneal melatonin (16). Dose-dependent anticonvulsive effects of melatonin were observed in convulsions induced by intracerebroventricular administration of quinolinic acid, kainate, glutamate, NMDA, and pentylenetetrazole (17). However, in most of the aforementioned seizure models, melatonin did not eradicate convulsions.…”

“…However, in most of the aforementioned seizure models, melatonin did not eradicate convulsions. Lapin, et al (17) reported longer seizure latencies or suppression of seizures as a function of melatonin administration.…”

The role of the melatoninergic system in epilepsy and comorbid psychiatric disorders

“…Moreover, data is controversial: indeed, exogenous melatonin has been reported to produce an anticonvulsant effect that was either strongly time-dependent (CostaLotufo et al, 2002;Golombek et al, 1992;Lapin et al, 1998) or independent from the time of day of administration (Champney et al, 1996;Mevissen et al, 1998). Exogenous melatonin and the secretion of the endogenous hormone at night can both protect neuronal cultures from apoptosis promoted by KA-induced oxidative stress (Manev et al, 1996).…”