S-Methylisothiourea sulfate is a potent, selective and competitive inhibitor of inducible nitric oxide synthase (iNOS). S-Methylisothiourea sulfate exerts beneficial effects in rodent models of septic shock.IC50 & Target: iNOSIn Vitro: S-Methylisothiourea sulfate is a competitive inhibitor of iNOS activity at the L-arginine site.
S-Methylisothiourea sulfate prevents the NO-mediated cytotoxic effect of LPS in cultured macrophages.
S-Methylisothiourea sulfate (100 nM-100 μM) exhibits inhibitory effects on LPS (ug/mL)-induced nitrite production in J774.2 macrophages and rat aortic vascular smooth muscle cells.
S-Methylisothiourea sulfate (up to 1 mM) does not inhibit the activity of xanthine oxidase, diaphorase, lactate dehydrogenase, monoamine oxidase, catalase, cytochrome P450, or superoxide dismutase.
In Vivo: S-Methylisothiourea sulfate (0.01-3 mg/kg; i.v.) dose-dependently reverses the hypotension and the vascular hyporeactivity to vasoconstrictor agents caused by endotoxin LPS in anesthetized rats.
S-Methylisothiourea sulfate (5 mg/kg; i.p.; given 2 hr after LPS; 10 mg/kg; i.p.) attenuates the rises in plasma alanine and aspartate aminotransferases, bilirubin, and creatinine and also prevents hypocalcaemia when measured 6 hr after administration of LPS.
S-Methylisothiourea sulfate (1 mg/kg; i.p.) improves 24-hr survival of mice treated with a high dose of LPS (60 mg/kg; i.p.).