Seizure susceptibility waxes and wanes in an apparently circadian mann
er in many epileptic patients. Fluctuations of melatonin concentration
with highest levels during the night and lowest levels in the early m
orning could be involved in this phenomenon. Therefore, the action of
melatonin on epileptic activity was tested. The experiments were carri
ed out on human temporal neocortical slices cut from tissue resected f
or surgical treatment of epilepsy. Autoradiographic studies were perfo
rmed on parallel slices with 100-120 pmol 2-[I-125]iodomelatonin/l in
the absence or presence of unlabelled melatonin. High-affinity binding
sites of melatonin could be demonstrated in layers II-V of the tempor
al cortex. The binding was saturable, specific and occurred with low c
apacity. In electrophysiological studies, epileptiform field potential
s were elicited by omission of Mg2+ from the superfu sate and recorded
from layers II-V. The frequency of occurrence of epileptiform field p
otentials was reduced to 0.5 of the initial value with application of
melatonin (10 and 100 nmol/l) in each case. This effect was reversible
upon washing. The findings favour the hypothesis that melatonin depre
sses epileptiform neuronal activity through specific neocortical recep
tors.