Molsidomine potentiates the protective activity of GYKI 52466, a non-NMDA antagonist, MK-801, a non-competitive NMDA antagonist, and riluzole against electroconvulsions in mice.
The influence of molsidomine, a donor of nitric oxide (NO), L-arginine, a substrate for NO synthesis, and N(G)-nitro-L-arginine (NNA), an inhibitor of NO synthase, on the protective activity of CGP 40116, GYKI 52466, MK-801, and riluzole against electroconvulsions was studied in mice. Molsidomine (100 mg kg(-1); i.p.) potentiated the protective activity of GYKI 52466, MK-801, and riluzole but did not influence the protection offered by CGP 40116. In contrast to molsidomine, L-arginine (500 mg kg(-1); i.p.) did not impair the protective activity of any anticonvulsant. In a dose of 40 mg kg(-1), NNA administered i.p. did not affect the protection offered by any excitatory amino acid antagonists and riluzole. Combinations of molsidomine with either GYKI 52466 or MK-801 as well as riluzole did not cause a memory deficit in the passive avoidance task. However, the combined treatment of molsidomine with these anticonvulsants resulted in a motor impairment quantified by the chimney test. The lack of effect of L-arginine and NNA on the protective activity of excitatory amino acid antagonists suggests that molsidomine-evoked alterations in the protection provided by some excitatory amino acid antagonists against electroconvulsions are independent of the NO pathway.
Tutka
Piotr
P
Department of Pharmacology and Toxicology, Medical University of Lublin, Jaczewskiego 8, PL-20-090 Lublin, Poland. tutkap@itsa.ucsf.edu
Olszewski
Krzysztof
K
Woźniak
Małgorzata
M
Kleinrok
Zdzisław
Z
Czuczwar
Stanisław J
SJ
Wielosz
Marian
M
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001569:Benzodiazepines; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004357:Drug Synergism; D004597:Electroshock / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D051379:Mice; D008981:Molsidomine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology; D019782:Riluzole / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; C061950:GYKI 52466; D001569:Benzodiazepines; D019335:Nitroarginine; D016291:Dizocilpine Maleate; D019782:Riluzole; D008981:Molsidomine; D019001:Nitric Oxide Synthase