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

This study evaluates the actions of the new ruthenium complexes trans-[RuCl 2(nic)(4)] (Complex I) and trans-[RuCl2(i-nic)(4)] (Complex LT) as antinoci ceptives, and their interaction with nitric oxide isoenzymes and with acety lcholine-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 th an the inducible form of the enzyme. Complex I was inactive. Both complexes failed to interfere with constitutive endothelial nitric oxide synthase be cause they did not change the mean arterial blood pressure of rats. The vas orelaxant 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 N-omega-nitro-L-arginine methyl ester (L-NAME) and N-G-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 an d Complex II, but not that of Complex I, were largely reversed by L-arginin e. Both complexes failed to affect the motor response of animals in the rot a-rod test and had no effect in the hot-plate assay. Together, these findin gs provide indications that the new ruthenium complexes, especially Complex LI and its derivatives, might be of potential therapeutic benefit in the m anagement of pain disorders. (C) 1999 Elsevier Science B.V. All rights rese rved.