S-methyl-L-Thiocitrulline hydrochloride

S-MTC (S-Methyl-L-thiocitrulline) dihydrochloride is a selective type I nitric oxide synthase (NOS) inhibitor.

Signaling Pathways >> Immunology/Inflammation >> NO Synthase

Research Areas >> Neurological Disease

NOS[1]

S-MTC dihydrochloride (10 or 100?μM) reduces cellular NO release in the absence of Aβ1-42. At 100?μM, S-MTC dihydrochloride decreases cell viability. S-MTC dihydrochloride (100?μM) significantly lowers nitrite production (11.2±1.1?μM) when compared to control (no NOS inhibitor exposure; 19.6±1.2?μM). Nitrite productions after Aβ1-42 and L-NOARG (100?μM) or Aβ1-42 and S-MTC dihydrochloride (100?μM) treatments are significantly lower than Aβ1-42 alone (33.5±2.0 and 34.5±1.6?μM, respectively). S-MTC dihydrochloride (100?μM) is able to significantly reduce nitrite production (25.2±1.1?μM) as compared to Aβ1-42 treatment alone (38.3±2.7?μM), when administered after Aβ1-42 at the 1?h time point. S-MTC dihydrochloride (100?μM) concentration decreases both MTT (87±1% of control) and NR (80±1% of control, respectively) levels. The co-administration of S-MTC dihydrochloride (100?μM) and Aβ1-42 significantly reverses the effects of Aβ1-42 alone (72±2% vs 61±2% of control)[1].

S-MTC dihydrochloride (S-methyl-L-thiocitrulline) is a selective neuronal NOS-inhibitor. Following pretreatment with S-MTC dihydrochloride (i.c.v.), the HBO2-induced antinociception is significantly antagonized. In Experiment #2, different groups of mice are pretreated with naltrexone hydrochloride (NTX) (3.0 mg/kg, i.p.), L-NAME (1.0 μg/mouse, i.c.v.), S-MTC dihydrochloride (1.0 μg/mouse, i.c.v.) or N5-(1-iminoethyl)-L-ornithine (L-NIO) (3.0 mg/kg, s.c.) 15-30 min prior to HBO2 treatment. The antinociceptive effect assessed 90 min after HBO2 treatment is completely abolished by NTX and L-NAME, antagonized by two-thirds by S-MTC dihydrochloride and largely unaffected by L-NIO (F=25.57, p<0.0001)[2]. At a dose of 0.3 mg/kg, S-MTC dihydrochloride (SMTC) causes a rise in mean blood pressure (BP). At doses of 1.0, 3.0 and 10 mg/kg, S-MTC dihydrochloride causes falls in heart rate, rises in BP and vasoconstriction in all three vascular beds[3].

[1]. Law A, et al. Neuroprotective and neurorescuing effects of isoform-specific nitric oxide synthase inhibitors, nitric oxide scavenger, and antioxidant against beta-amyloid toxicity. Br J Pharmacol. 2001 Aug;133(7):1114-24.  

[2]. Zelinski LM, et al. A prolonged nitric oxide-dependent, opioid-mediated antinociceptive effect of hyperbaric oxygenin mice. J Pain. 2009 Feb;10(2):167-72.  

[3]. Wakefield ID, et al. Comparative regional haemodynamic effects of the nitric oxide synthase inhibitors, S-methyl-L-thiocitrulline and L-NAME, in conscious rats. Br J Pharmacol. 2003 Jul;139(6):1235-43.