Influence of melatonin upon the protective action of conventional anti-epileptic drugs against maximal electroshock in mice.
Melatonin (50 mg/kg; 60 min before the test) significantly raised the electroconvulsive threshold in mice. The protective action of melatonin (50 mg/kg) in the electroconvulsive threshold test was reversed by aminophylline, picrotoxin and bicuculline. Melatonin at the subconvulsive dose of 25 mg/kg potentiated the anticonvulsive activity of carbamazepine and phenobarbital (ED50 values were significantly decreased from 12.1 to 8.3 and from 18.9 to 11.8 mg/kg, respectively). No potentiation was observed in the case of valproate and diphenylhydantoin (their ED50s were changed from 253 to 249 and from 10.3 to 9.7 mg/kg, respectively). Melatonin did not influence the plasma or brain levels of anti-epileptics studied, so a pharmacokinetic interaction is not probable. Melatonin (25 mg/kg) alone and its combinations with carbamazepine or phenobarbital, providing a 50% protection against maximal electroshock, were devoid of significant motor adverse effects, but caused strong long-term memory deficit. Consequently, it does not seem to be a good candidate for the treatment of epilepsy.
Borowicz
K K
KK
Department of Pharmacology and Toxicology, Lublin Medical University School, Poland.
Kamiński
R
R
Gasior
M
M
Kleinrok
Z
Z
Czuczwar
S J
SJ
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004347:Drug Interactions; D004597:Electroshock; D005260:Female; D008550:Melatonin / Q000009:adverse effects / Q000494:pharmacology*; D051379:Mice; D011597:Psychomotor Performance / Q000187:drug effects; D012640:Seizures / Q000517:prevention & control*
D000927:Anticonvulsants; C027513:N(6)-cyclohexyladenosine; D008550:Melatonin; D000241:Adenosine