Although
melatonin is approved only for the treatment of
jet-lag syndrome and some types of
insomnia, clinical data suggest that it is effective in the adjunctive
therapy of
osteoporosis,
cataract,
sepsis,
neurodegenerative diseases,
hypertension, and even
cancer.
Melatonin also modulates the electrical activity of neurons by reducing glutamatergic and enhancing
GABA-ergic neurotransmission. The indoleamine may also be metabolized to
kynurenic acid, an endogenous
anticonvulsant. Finally, the
hormone and its metabolites act as
free radical scavengers and
antioxidants. The vast majority of experimental data indicates
anticonvulsant properties of the
hormone.
Melatonin inhibited audiogenic and electrical
seizures, as well as reduced convulsions induced by
pentetrazole,
pilocarpine,
L-cysteine and
kainate. Only a few studies have shown direct or indirect proconvulsant effects of
melatonin. For instance,
melatonin enhanced low Mg2+-induced epileptiform activity in the hippocampus, whereas
melatonin antagonists delayed the onset of
pilocarpine-induced
seizures. However, the relatively high doses of
melatonin required to inhibit experimental
seizures can induce some undesired effects (e.g., cognitive and motor impairment and decreased body temperature). In humans,
melatonin may attenuate
seizures, and it is most effective in the treatment of juvenile
intractable epilepsy. Its additional benefits include improved physical, emotional, cognitive, and social functions. On the other hand,
melatonin has been shown to induce electroencephalographic abnormalities in patients with
temporal lobe epilepsy and increase seizure activity in neurologically disabled children. The
hormone showed very low toxicity in clinical practice. The reported adverse effects (nightmares,
hypotension, and
sleep disorders) were rare and mild. However, more placebo-controlled, double-blind randomized clinical trials are needed to establish the usefulness of
melatonin in the adjunctive treatment of
epilepsy.