Melatonin's Role as an Anticonvulsant and Neuronal Protector: Experimental and Clinical Evidence

Abstract

The pineal gland classically has been considered as a vestigial and mystic organ. In the last decades, and with the incorporation of new methodologic procedures, it could be proved that it also has physiologic actions that vary depending on the level of the phylogenetic scale. Its best-known secretion, melatonin, has been related to many different actions, such as sleep promotion, control of biologic rhythms, hormonal inhibition, and an inhibiting action on central nervous system regulation mechanisms. In animal experimentation, there are papers even accepting an anticonvulsant effect. In humans, evidence is reduced to few experiences. In addition to this clinical experience, there is other evidence that clearly relates melatonin to convulsive phenomena. This relationship must be mediated by the following mechanisms attributed to melatonin: altered brain GABAergic neurotransmission, its known interaction with benzodiazepinic brain receptors, through tryptophan metabolite activity (kynurenine, kynurenic acid), or even by its efficacy as a free-radical scavenger.

Temporal distributions of seizure occurrence from various epileptogenic regions

“…38 Melatonin secretion peaks in the dark portion of the day and has been found to increase hippocampal excitability [39][40][41] but acts as an anticonvulsant elsewhere. 42 Histamine, dopamine, serotonin, norepinephrine, and the components of the hypothalamic-pituitaryadrenal axis are a few of the other factors that have been found to both modify epileptic activity and vary in circadian fashion in at least some neural regions. [43][44][45][46][47][48] The variation in no single factor coincides with the regional and temporal patterns we report; it is instead likely that the complex interaction of many circadian and exogenous processes result in periods of time when particular neural regions are particularly vulnerable to epileptic episodes.…”

Diurnal and Seasonal Occurrence of Febrile Seizures

“…3 Melatonin (N-acetyl-5-methoxytryptamine) is secreted mostly at night and in the dark, and exposure to light reduces its secretion. 4 Melatonin seems to possess some anticonvulsant effects [5][6][7][8] ; some studies suggest an association between melatonin and the occurrence of febrile seizures 9-11 also as an explanation to the epidemiology of febrile seizures. 10,11 Many types of epileptic seizure occur according to a specific circadian rhythm.…”

Assessing the efficacy of melatonin to curtail benzodiazepine/Z drug abuse

“…see [71]). Such anticonvulsant action of melatonin could be attributed to both MT 1 and MT 2 receptors [25,[72][73][74][75][76] and similar anti-seizure effects were observed with the MT 1 / MT 2 agonist ramelteon [77]. These antiexcitatory actions are also related to the anxiolytic, antihyperalgesic and antinociceptive effects of melatonergic agents [78][79][80][81][82][83].…”