2-Nicotinamidoethyl acetate (SG-209) is a potassium channel opener: structure activity relationship among nicorandil derivatives.

T Ishibashi, M Hamaguchi, S Imai

Index: Naunyn Schmiedebergs Arch. Pharmacol. 344 , 235-239, (1991)

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Abstract

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.