生物活性

• 靶点

  nNOS (bovine) Ki:15nM

  eNOS Ki:39nM

  iNOS (murine) Ki:4.4μM

• 描述Nitric oxide synthase (NOS) is an enzyme responsible for the production of nitric oxide (NO) from L-arginine. L-NAME HCl is an inhibitor for bovine brain NOS and mouse macrophage NOS with K_i values of 15 nM and 4.4 μM, respectively^[1]. In rMC-1 cells, the accumulation of NO induced by glucose (25 mM) was inhibited by 1 mM L-NAME HCl. The treatment of L-NAME HCl at 1 mM also led to significantly decreased cell death in glucose-stimulated rMC-1 cells. Elevated production of PGE₂ in BREC cells was significantly suppressed by 1 mM L-NAME HCl^[2]. With the presence of 30 μM L-arginine and 100 μM NADPH, L-NAME HCl at 0.1 – 100 μM dose-dependently inhibited the formation of cyclic GMP in endothelial cytosol with an IC₅₀ value of 3.1 μM. It also inhibited [³H]-citrulline formation with an IC₅₀ value of 0.09 μM. L-NAME HCl at 0.1 – 300 μM induced endothelium-dependent contraction of rings of rat aorta with an EC₅₀ value of 26 μM in the presence of 10 nM phenylephrine. The relaxation of rings of rat aorta was inhibited by 0.1 – 10 μM L-NAME HCl at a dose-dependent manner with an IC₅₀ value of 0.54 μM. In Wistar rats, i.v. administration of L-NAME HCl (0.03 – 300 mg/kg) dose-dependently increased the mean arterial blood pressure with an EC₅₀ value of 2.4 mg/kg, and the highest blood pressure induced by L-NAME HCl was 44.1 mmHg. The same treatment of L-NAME HCl also resulted in bradycardia at a concentration-dependent manner^[3].
• 作用机制L-NAME HCl is a soluble methyl ester that inhibits NOS. Intracellular esterases convert a variable and unknown fraction of L-NAME to L-NNA, which tightly but reversibly binds to NOS, competing with L-arginine^[4].

• 动物研究
  剂量	Rat: 40 mg/kg[5] (p.o.); 200 mg/kg[6] (i.p.) Mice: 10 mg/kg - 60 mg/kg[7] (i.p.)
  给药途径	p.o., i.p.