Antinociceptive properties and nitric oxide synthase inhibitory action of new ruthenium complexes.
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 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 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.
Beirith
A
A
Department of Pharmacology, Centre of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Brazil.
Creczynski-Pasa
T B
TB
Bonetti
V R
VR
Konzen
M
M
Seifriz
I
I
Paula
M S
MS
Franco
C V
CV
Calixto
J B
JB
D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007527:Isoenzymes / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019335:Nitroarginine / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D017975:Ruthenium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000700:Analgesics; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D017975:Ruthenium Compounds; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; C038365:ruthenium chloride; D019331:NG-Nitroarginine Methyl Ester