Nitric oxide inhibitors

Several in vitro and in vivo models mentioned previously are used by various laboratories to study the best methods for preventing superantigen-induced shock. Therapeutic agents such as nitric oxide inhibitors can experimentally decrease SEA and SEB effects by subsequently inhibiting IL-1, IL-2, IE-6, TNF, and IFN7... 

Izumi, Y., Benz, A.M., Clifford, D.B. and Zorumski, C.F. (1991a). Nitric oxide inhibitors attenuate Al-methyl-D-aspartate excitotoxicity in rat hippocampal slices. Neurosci. Lett. 135 227-230. 

D. Clinical Applications of Nitric Oxide Inhibitors and Donors While inhibitors of nitric oxide synthesis are of great research interest, none are currently in clinical use. Nitric oxide can be inactivated by heme, but application of this approach is in preclinical research. 

In addition to the above drugs, nitric oxide inhibitor (Lubeluzole), opioid antagonist (Nalmefene), serotonin agonist (Repinotan), and sodium channel blocker... 

Fig. 4. Effect of n-3 and n-6 polyunsaturated fatty acids (PUFA) on abnormal contraction in hypertensive vessels. Aortic rings from the spontaneously hypertensive rats (8-12 mo old) were incubated in the presence of nitric oxide inhibitor [Nco-nitro-i-argi-nine (NOLA) l 0 " M] for 60 min to unmask the abnormal contraction as described previously (13,18). Purified fatty acids were added cumulatively in small volumes (<15 pL), and the changes in tension monitored for a further 30-min period. DHA, docosahexaenoic acid EPA, eicosapentaenoic acid ALA, a-linolenic acid LA, linoleic acid. Vehicle (ethanol) controls were conducted and showed minimal effect on contraction. Results are means + SEM, n = 4-6 experiments.

Moniruzzaman, M. Kamiya, N. Goto, M. (2010). Activation and stabilization of enzymes in ionic liquids. Org, Biomol. Chem., 8,13, 2887-2899 Nagaoka, T. Banskota, A.H. Tezuka, Y. Midorikawa, K. Matsushige, K. Kadota, S. (2003). Caffeic acid phenethyl ester (cape) analogues Potent nitric oxide inhibitors from the netherlands propolis. Biol Pharm. Bull, 26,4,487-491 Nara, S.J. Harjani, J.R. Salunkhe, M.M. (2002). Lipase-catalysed transesterification in ionic liquids and organic solvents A comparative study. Tetrahedron Lett., 43, 16, 2979-2982... 

Amin-Hanjani S, StagUano NE, Yamada M, Huang PL, Liao JK, Moskowitz MA. Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endotheUal nitric oxide synthase in mice. Stroke 2001 32 980-986. 

As 1,2,5-thiadiazole analogues, potent HlV-1 reverse transcriptase inhibitors, some simple 1,2,5-oxadiazoles, compounds 4-6 (Fig. 9), have been synthesized using the traditional Wieland procedure as key for the heterocycle formation [121]. Such as thiadiazole parent compounds, derivative with chlorine atoms on the phenyl ring, i.e., 5, showed the best anti-viral activity. Selectivity index (ratio of cytotoxic concentration to effective concentration) ranked in the order of 5 > 6 > 4. The activity of Fz derivative 6 proved the N-oxide lack of relevance in the studied bioactivity. These products have been claimed in an invention patent [122]. On the other hand, compound 7 (Fig. 9) was evaluated for its nitric oxide (NO)-releasing property (see below) as modulator of the catalytic activity of HlV-1 reverse transcriptase. It was found that NO inhibited dose-dependently the enzyme activity, which is hkely due to oxidation of Cys residues [123]. 

Kanner, J., Harel, S. and Granit, R (1992). Nitric oxide, an inhibitor of lipid oxidation by lipoxygenase cyclooxygenase and hemoglobin. Lipids 27, 46—49. 

Mulligan, M.S., Moncada, S. and Ward, P.A. (1992). Protective eflfect of inhibitors of nitric oxide synthase in immune complex-induced vasculitis. Br. J. Pharmacol. 107, 1159-1162. 

A relationship between polyol pathway activity and reduction in endothelium-dependent relaxation in aorta from chronic STZ-diabetic rats has recently been reported (Cameron and Cotter, 1992). In agreement with several previous studies (Oyama et al., 1986 Kamata et al., 1989), endothelial-dependent relaxation was defective in the diabetic rats but the deficit was prevented by prior treatment with an AR inhibitor. The mechanism underlying the defect has been speculated to be due to decreased production of endothelium-derived relaxing factor (EDRF) or nitric oxide, NO (Hattori et al., 1991). It has been speculated that these vascular abnormalities may lead to diminished blood flow in susceptible tissues and contribute to the development of some diabetic complications. NO is synthesized from the amino-acid L-arginine by a calcium-dependent NO synthase, which requires NADPH as a cofactor. Competition for NADPH from the polyol pathway would take place during times of sustained hyperglycaemia and... 

Buisson, A., Margaill, L, Callebert, J., Plotkine, M. and Boulu, R.G. (1993). Mechanism involved in the neuroprotective activity of a nitric oxide synthase inhibitor during focal cerebral ischemia. J. Neurochem. 61, 690-696. 

Hydroxyurea is a ribonucleotide reductase inhibitor that prevents DNA synthesis and traditionally has been used in chemotherapy regimens. Studies in the 1990s also found that hydroxyurea increases HbF levels as well as increasing the number of HbF-containing reticulocytes and intracellular HbF. Other beneficial effects of hydroxyurea include antioxidant properties, reduction of neutrophils and monocytes, increased intracellular water content leading to increased red cell deformability, decreased red cell adhesion to endothelium, and increased levels of nitric oxide, which is a regulator involved in physiologic disturbances.22... 

Dzoljic, E., van Leeuwen, R., de Vries, R. Dzoljic, M. R. (1997). Vigilance and EEC power in rats effects of potent inhibitors of the neuronal nitric oxide synthase. Naunyn Schmiedebergs Arch. Pharmacol. 356, 56-61. 

Monti, J. M., Hantos, H., Ponzoni, A., Monti, D. Banchero, P. (1999). Role of nitric oxide in sleep regulation effects of L-NAME, an inhibitor of nitric oxide synthase, on sleep in rats. Behav. Brain Res. 100, 197-205. 

Ribeiro, A. C. Kapas, L. (2005). Day- and nighttime injection of a nitric oxide synthase inhibitor elicits opposite sleep responses in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289, R521-31. 

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