The role of nitric oxide in chemically- and electrically-induced seizures in mice.
The effect of the nitric oxide synthase (NOS) inhibitors N-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) on seizures induced by N-methyl-D-aspartate (NMDA), pilocarpine (PIL) and pentylenetetrazol (PTZ), as well as on the electroconvulsive threshold was studied in mice. It was found that L-NAME and 7-NI decreased the dose of NMDA necessary to produce clonic convulsions in 50% of animals (CD50). Such a proconvulsant effect was not observed in mice pretreated with N-nitro-D-arginine methyl ester (D-NAME), an inactive isomer of L-NAME. Neither L-NAME nor 7-NI affected the convulsions induced by PIL (clonic seizures) or PTZ (clonic and tonic seizures), having no effect on their CD50 values. Similarly, neither NOS inhibitor affected the electroshock threshold. These results, together with some literature data, indicate that nitric oxide (NO) may be regarded as an anticonvulsant substance in relation to seizures induced by NMDA and other excitatory amino acids, but not by other agents, in mice.
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
E
E
Przegaliñski
L
L
Baran
J
J
Siwanowicz
D000818:Animals; D003292:Convulsants; D004597:Electroshock; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D018721:Muscarinic Agonists; D016202:N-Methylaspartate; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010433:Pentylenetetrazole; D010862:Pilocarpine; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*
D003292:Convulsants; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D007191:Indazoles; D018721:Muscarinic Agonists; D010862:Pilocarpine; D009569:Nitric Oxide; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester; D010433:Pentylenetetrazole