Ishibashi T, Hamaguchi M, Imai S
Department of Pharmacology, Niigata University School of Medicine, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1991 Aug;344(2):235-9. doi: 10.1007/BF00167224.
The mechanism of the vasodilating action of 2-nicotinamidoethyl acetate (SG-209), a derivative of nicorandil, was examined in the isolated rabbit aorta. Comparison was made using 2-nicotinamidoethyl alcohol (SG-86) and 2-nicotinamidoethyl nitrate (nicorandil; SG-75) to reveal any structure-activity relationships. SG-209 and nicorandil caused concentration-dependent relaxation in preparations precontracted with phenylephrine (10(-7) mol/l), while SG-86 produced a relaxation only at very high concentrations. The pD2 values (-log[EC50]) of SG-209 and nicorandil were 3.59 +/- 0.07 and 5.95 +/- 0.10, respectively. The vasorelaxant activity of nicorandil was associated with significant increases in cyclic GMP content, while that of SG-209 was not. Methylene blue (10(-5) mol/l) attenuated the relaxant effect of nicorandil, but had no effect on that of SG-209. Furthermore, the relaxant effect of nicorandil was not affected by glibenclamide (10(-5) mol/l), whilst the relaxant effect of SG-209 was abolished by this compound. In the presence of methylene blue (10(-5) mol/l), however, glibenclamide (10(-5) mol/l) attenuated the relaxant effect of higher concentrations of nicorandil (greater than or equal to 10(-5) mol/l). These results indicate that the relaxant effect of SG-209 is mostly if not exclusively due to the activation of potassium channels, while this action contributes to the vasodilating action of nicorandil only at higher concentrations.
在离体兔主动脉中研究了尼可地尔衍生物2-烟酰胺基乙酸乙酯（SG-209）的血管舒张作用机制。使用2-烟酰胺基乙醇（SG-86）和2-烟酰胺基硝酸乙酯（尼可地尔；SG-75）进行比较，以揭示任何构效关系。SG-209和尼可地尔在预先用去氧肾上腺素（10⁻⁷mol/L）预收缩的制剂中引起浓度依赖性舒张，而SG-86仅在非常高的浓度下才产生舒张作用。SG-209和尼可地尔的pD2值（-log[EC50]）分别为3.59±0.07和5.95±0.10。尼可地尔的血管舒张活性与环鸟苷酸含量的显著增加有关，而SG-209则不然。亚甲蓝（10⁻⁵mol/L）减弱了尼可地尔的舒张作用，但对SG-209的舒张作用没有影响。此外，尼可地尔的舒张作用不受格列本脲（10⁻⁵mol/L）的影响，而SG-209的舒张作用则被该化合物消除。然而，在亚甲蓝（10⁻⁵mol/L）存在的情况下，格列本脲（10⁻⁵mol/L）减弱了较高浓度尼可地尔（大于或等于10⁻⁵mol/L）的舒张作用。这些结果表明，SG-209的舒张作用即使不是完全也是主要由于钾通道的激活，而这种作用仅在较高浓度下才对尼可地尔的血管舒张作用有贡献。
