Antinociceptive properties and nitric oxide synthase inhibitory action of new ruthenium complexes
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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ABSTRACT: From the thousands of years, metal compounds have been used in medicine for treatment of various diseases including various types of cancers. Ruthenium was seen as a promising metal due to its similar kinetics to platinum and its lower toxicity. Therefore, we aimed to evaluate the newer mononuclear ruthenium (II) compounds for antinociceptive and antitumor activities. Ruthenium (II) compounds were evaluated for antinociceptive and antitumor activity using the various in vitro and in vivo models. The compounds were injected to mice at concentrations of 1 and 2 mg kg(-1) intraperitoneally and were screened for antinociceptive activity, and the antiproliferative effect was evaluated against murine leukemia cells (L1210), human T-lymphocyte cells (CEM) and human cervix carcinoma cells (HeLa) using MTT assay. The results for antitumor activity clearly indicated that compound R1 was potent cytotoxic agent than R2 with IC50 values ranging from 4-6 μM for R1, whereas IC50 values for compound R2 ranging from 65-103 μM. The compounds have shown a significant anti-inflammatory effect in carrageenan and dextran models but do not having the central analgesic activity, this indicating that the antinociceptive activity is related to the peripheral nervous system. The results for 5-Lipoxygenase (5-LOX) activity showed that both R1 and R2 compounds were found to be significant 5-LOX inhibitory activity with IC50 values of 14.35 μg ml(-1) and 29.24 μg ml(-1) respectively. These findings concluded that the new ruthenium compounds might be the promising antiproliferative agents as these compounds showing significant 5-LOX inhibitory activity and potential agents in the management of pain related disorders.Journal of research in medical sciences 03/2013; 18(3):215-21. · 0.68 Impact Factor
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ABSTRACT: In experiments on mongrel albino male mice with a nidus of tonic pain created by subcutaneous injection of 5% formalin solution into the hindlimb, we estimated changes in nociceptive behavioral reaction (licking the pain nidus) elicited by i.p. injections of compounds modulating the system of nitric oxide (NO): a blocker of NO synthase, N-nitro-L-arginine (L-NAME), and activator of NO synthesis, L-arginine (L-Arg), as well as NO donors: sodium nitroprusside (SNP) and sodium nitrate (SN). After injections of L-NAME, L-Arg, and SN, the intensity of the nociceptive behavioral reaction dropped by 55-21%, as compared with the control. In contrast, SN significantly increased the intensity of this reaction. Mechanisms responsible for modulation of the nociceptive behavioral reaction with the involvement of NO and specific features of the effects of different NO donors on this reaction (related to a complex nature of these effects) are discussed.Neurophysiology 08/2001; 33(5):314-321. · 0.38 Impact Factor
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ABSTRACT: Chronic pain affects a high percentage of the general population. Traditional therapies based upon non-steroidal anti-inflammatory drugs (NSAIDs), opioids and co-analgesic therapies, such as antidepressant or anti-epileptic drugs, are often relatively ineffective in treating chronic pain. In addition, the low therapeutic indexes and, in particular, the often-intolerable side effect profiles of conventional compounds, limit their usefulness, especially in the elderly population. Despite intensive research, until recently there was little change in the classes of drugs available to treat chronic pain clinically. This was partly due to a failure to understand which physiological processes are important in mediating clinical chronic pain. Recently, however, greater understanding of the neurophysiology critical to chronic pain development has lead to the development of numerous alternative pharmacological strategies. This review article outlines the physiological processes occurring in chronic pain, highlights some of the approaches recently developed and mentions a number of drugs currently under development that aim to provide safer and more effective analgesia for chronic pain. These include COX-2 inhibitors, gabapentin, capsaicin, new opioid strategies, neurokinin-1 (NK-1) antagonists, cannabinoid receptor agonists, neuronal nitric oxide synthase (nNOS) inhibitors and NMDA receptor antagonists, as well as a number of other therapeutic strategies in development.02/2005; 5(4):385-413.