(S)-Methylisothiourea (S-Methylisothiourea) Sulfate (SMT) is a potent, selective and competitive inhibitor of inducible nitric oxide synthase (iNOS). 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. SMT is equipotent with MeArg in inhibiting the endothelial, constitutive isoform of NOS in vitro and causes increases in blood pressure similar to those produced by MeArg in normal rats. SMT, however, 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 SMT (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. SMT (1 mg/kg, i.p.) improves 24-hr survival of mice treated with a high dose of LPS (60 mg/kg, i.p.)[1]. In addition, S-methylisothiourea (SMT) had anti-inflammatory effects in treating herpes simplex encephalitis in mice, and SMT also induced apoptosis of herpes simplex virus (HSV-1)-infected microglial cells[2]. SMT (30 mg/kg) attenuates the MIA-induced pain and histopathological changes in the knee joint. The antinociceptive and antiarthritic effects of SMT were mediated by inhibiting cartilage damage and suppression of NO in synovial fluid[3]. HOT (Hyperbaric oxygen treatment) and SMT together were significantly more effective in preventing weight loss and in reducing inflammation and the severity of colitis histology when compared with HOT and SMT separately[4].
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