The influence of L-NG-nitroarginine methyl ester, an inhibitor of nitric oxide synthase, upon the anticonvulsive activity of conventional antiepileptic drugs against maximal electroshock in mice.
NG-Nitro-L-arginine methyl ester (L-NAME, an unspecific nitric oxide synthase inhibitor), applied at 1 and 40 mg/kg, did not influence the electroconvulsive threshold, but impaired the anticonvulsant activity of valproate (at 40 mg/kg) and phenobarbital (at 1 and 40 mg/kg). No effect was observed in the case of carbamazepine and diphenylhydantoin. The effect of L-NAME upon the protective activity of phenobarbital was not reversed by L-arginine (500 mg/kg), a source of endogenous nitric oxide. Moreover, this nitric oxide synthase inhibitor did not alter the plasma levels of antiepileptic drugs studied, so a pharmacokinetic interaction is not probable. L-NAME per se (40 mg/kg) caused a moderate motor impairment but did not affect long-term memory. The combined treatment of L-NAME and antiepileptic drugs (providing a 50% protection against maximal electroshock) resulted in motor disturbances. On the other hand, mice performed the memory task better upon combined treatment of antiepileptic drugs with L-NAME compared to antiepileptic drugs alone. A 4-day administration of L-NAME, similarly to acute injections, decreased the protective action of phenobarbital but not that of diphenylhydantoin. The results indicate that L-NAME is able to reduce the protective activity of some conventional antiepileptics and this effect may be not associated with impaired synthesis of nitric oxide.
Borowicz
K K
KK
Department of Pharmacology and Toxicology, Lublin Medical University School, Poland.
Starownik
R
R
Kleinrok
Z
Z
Czuczwar
S J
SJ
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D002220:Carbamazepine / Q000097:blood / Q000494:pharmacology; D004336:Drug Antagonism; D004597:Electroshock; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D008568:Memory / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010634:Phenobarbital / Q000097:blood / Q000494:pharmacology; D010672:Phenytoin / Q000097:blood / Q000494:pharmacology; D012640:Seizures / Q000503:physiopathology; D014635:Valproic Acid / Q000097:blood / Q000494:pharmacology
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D010634:Phenobarbital