Anticonvulsant activity of melatonin against seizures induced by quinolinate, kainate, glutamate, NMDA, and pentylenetetrazole in mice.
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.
Lapin
I P
IP
Laboratory of Psychopharmacology, Bekhterev Psychoneurological Research Institute, St. Petersburg, Russia.
Mirzaev
S M
SM
Ryzov
I V
IV
Oxenkrug
G F
GF
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D003292:Convulsants / Q000037:antagonists & inhibitors* / Q000633:toxicity; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000633:toxicity; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000633:toxicity; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors / Q000633:toxicity; D017378:Quinolinic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*
D000927:Anticonvulsants; D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D016202:N-Methylaspartate; D017378:Quinolinic Acid; D008550:Melatonin; D007608:Kainic Acid; D010433:Pentylenetetrazole