Antinociceptive properties and nitric oxide synthase inhibitory action of new ruthenium complexes

Department of Pharmacology, Centre of Biological Sciences, Federal University of Santa Catarina, Rua Ferreira Lima, 82, Florianópolis, SC, 88015-420, Brazil; Department of Physiology, Federal University of Santa Catarina, Florianópolis, SC, 88015-420, Brazil; Department of Chemistry, Federal University of Santa Catarina, Florianópolis, SC, 88015-420, Brazil
European Journal of Pharmacology (Impact Factor: 2.59). 04/1999; DOI: 10.1016/S0014-2999(99)00095-3

ABSTRACT This study evaluates the actions of the new ruthenium complexes trans-[RuCl2(nic)4] (Complex I) and trans-[RuCl2(i-nic)4] (Complex II) as antinociceptives, and their interaction with nitric oxide isoenzymes and with acetylcholine-induced relaxation of rat and rabbit aorta. Complex II inhibited, in a graded manner, neuronal and inducible nitric oxide (NO) synthase, and was about two fold more effective in inhibiting the neuronal NO synthase than the inducible form of the enzyme. Complex I was inactive. Both complexes failed to interfere with constitutive endothelial nitric oxide synthase because they did not change the mean arterial blood pressure of rats. The vasorelaxant effect of acetylcholine was markedly antagonised by the Complexes I and II in rings of both rat and rabbit aorta. Complexes I and II, given intraperitoneally, like Nω-nitro-l-arginine methyl ester (l-NAME) and NG-nitro-l-arginine (l-NOARG), inhibited, in a graded manner, both phases of the pain response induced by formalin. The actions of l-NAME, l-NOARG and Complex II, but not that of Complex I, were largely reversed by l-arginine. Both complexes failed to affect the motor response of animals in the rota-rod test and had no effect in the hot-plate assay. Together, these findings provide indications that the new ruthenium complexes, especially Complex II and its derivatives, might be of potential therapeutic benefit in the management of pain disorders.

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