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.
Department of Pharmacology and Toxicology, Medical University of Lublin, Jaczewskiego 8, PL-20-090 Lublin, Poland. tutkap@itsa.ucsf.edu
Piotr
P
Tutka
Krzysztof
K
Olszewski
Małgorzata
M
Woźniak
Zdzisław
Z
Kleinrok
Stanisław J
SJ
Czuczwar
Marian
M
Wielosz
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