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

• Published in: European neuropsychopharmacology Vol. 12; no. 4; pp. 321 - 326
• Main Authors: Tutka, Piotr, Olszewski, Krzysztof, Woźniak, Małgorzata, Kleinrok, Zdzisław, Czuczwar, Stanisław J, Wielosz, Marian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2002
• Subjects: Animals; Anti-Anxiety Agents - pharmacology; Benzodiazepines; Dizocilpine Maleate - pharmacology; Drug Synergism; Electroshock - adverse effects; Enzyme Inhibitors - pharmacology; Epilepsy; Excitatory amino acid antagonists; Excitatory Amino Acid Antagonists - pharmacology; Mice; Molsidomine; Molsidomine - pharmacology; Motor Activity - drug effects; NG-Nitro- l-arginine; Nitric oxide; Nitric Oxide Synthase - antagonists & inhibitors; Nitroarginine - pharmacology; Receptors, Glutamate - drug effects; Receptors, Glutamate - physiology; Riluzole - pharmacology; Seizure; Seizure; Molsidomine; N G-Nitro- l-arginine; Nitric oxide; Epilepsy; Excitatory amino acid antagonists
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/S0924-977X(02)00046-9

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.