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].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  mouse BV2 cells	-	Function assay	24 h	Inhibition of Nitric oxide synthase activity in mouse BV2 cells assessed as LPS-induced NO production after 24 hrs by Griess reaction, IC50=18.9 μM	21377368
  mouse RAW264.7 cells	-	Function assay	17-20 h	Antiinflammatory activity in mouse RAW264.7 cells assessed as inhibition of IFN-gamma/LPS-stimulated nitric oxide production after 17 to 20 hrs by Griess assay, IC50=27.13 μM	19359068

• 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.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03684213	Cardiovascular Diseases ... more >> Cardiovascular Risk Factor Vasoconstriction Collapse <<	Phase 1	Not yet recruiting	August 31, 2019	United States, Texas ... more >> Engineering Research Building Arlington, Texas, United States, 76019 Collapse <<
  NCT00835224	Orthostatic Hypotension ... more >> Spinal Cord Injury Collapse <<	Phase 2	Completed	-	United States, New York ... more >> VA Medical Center, Bronx Bronx, New York, United States, 10468 Collapse <<
  NCT00835224	-	-	Completed	-	-

• 参考文献

• [1] Furfine ES, Harmon MF, et al. Selective inhibition of constitutive nitric oxide synthase by L-NG-nitroarginine. Biochemistry. 1993;32(33):8512-7.

  [2] Du Y, Sarthy VP, Kern TS. Interaction between NO and COX pathways in retinal cells exposed to elevated glucose and retina of diabetic rats. Am J Physiol Regul Integr Comp Physiol. 2004;287(4):R735-41.

  [3] Rees DD, Palmer RM, et al. Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol. 1990;101(3):746-52.

  [4] Griffith OW, Kilbourn RG. Nitric oxide synthase inhibitors: amino acids. Methods Enzymol. 1996.