S-Methylisothiourea sulfate is a competitive inhibitor of iNOS activity at the L-arginine site. The effect of S-Methylisothiourea sulfate on iNOS activity can be reversed by excess L-arginine in a concentration-dependent manner. 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. 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[1].

S-Methylisothiourea sulfate dose-dependently reverses (0.01-3 mg/kg) the hypotension and the vascular hyporeactivity to vasoconstrictor agents caused by endotoxin [bacterial lipopolysaccharide (LPS), 10 mg/kg, i.v.] in anesthetized rats. Moreover, therapeutic administration of 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.)[1].