title: 2-Nicotinamidoethyl acetate (SG-209) is a potassium channel opener: structure activity relationship among nicorandil derivatives.
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.
authors.affiliation: Department of Pharmacology, Niigata University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ishibashi
authors.forename: M
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: S
authors.initials: S
authors.lastname: Imai
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000032:analysis; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011817:Rabbits; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D015221:Potassium Channels; D014665:Vasodilator Agents; D010656:Phenylephrine; D009536:Niacinamide; D020108:Nicorandil; C030731:N-(2-hydroxyethyl)nicotinamide; C035663:SG 209; D006152:Cyclic GMP; D005905:Glyburide; D008751:Methylene Blue