Effect of nitric oxide synthase inhibitors and molsidomine on the anticonvulsant activity of some antiepileptic drugs.
The present study examined effects of the two nitric oxide synthase (NOS) inhibitors, N-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), as well as of the NO donor molsidomine on the anticonvulsant activity of conventional antiepileptic drugs (diphenylhydantoin and carbamazepine) and competitive (CGP 37,849) and non-competitive (dizocilpine) NMDA receptor antagonists against the maximal electroshock in mice. It was found that L-NAME (25 and 50 mg/kg) did not affect the anticonvulsant activity of either drug, having had no influence on their anticonvulsive ED50 values. 7-NI (50 and 100 mg/kg) reduced the anticonvulsive ED50 (augmentation of the anticonvulsant activity) of CGP 37,849 and dizocilpine, raised the anticonvulsive ED50 (attenuation of the anticonvulsant activity) of diphenylhydantoin and had no influence on the anticonvulsant effect of carbamazepine. At the same time, augmentation of the anticonvulsant activity (reduction of the ED50 values) of diphenylhydantoin, carbamazepine and CGP 37,849, but not of dizocilpine, was observed after molsidomine (100-150 mg/kg). Moreover, 7-NI (100 mg/kg) and molsidomine (100 and 150 mg/kg), but not L-NAME (25 and 50 mg/kg), raised the threshold for electroconvulsions. The obtained results indicate that alterations in the anticonvulsant activity of the investigated drugs evoked by 7-NI and mosidomine, may result from non-specific effects of the NOS inhibitor and the NO donor, having no connection with the brain NO pathway.
Baran
L
L
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Siwanowicz
J
J
Przegaliński
E
E
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004597:Electroshock; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008981:Molsidomine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010672:Phenytoin / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012640:Seizures / Q000503:physiopathology*
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007191:Indazoles; D016194:Receptors, N-Methyl-D-Aspartate; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D009569:Nitric Oxide; D002220:Carbamazepine; D010672:Phenytoin; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D008981:Molsidomine; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester