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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 344, Issue 2, pp 235–239 | Cite as

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

  • Takaharu Ishibashi
  • Masami Hamaguchi
  • Shoichi Imai
Article

Summary

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 (≥ 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.

Key words

SG-209 Nicorandil SG-86 Cyclic GMP Isolated rabbit aorta 

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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Takaharu Ishibashi
    • 1
  • Masami Hamaguchi
    • 1
  • Shoichi Imai
    • 1
  1. 1.Department of PharmacologyNiigata University School of MedicineNiigataJapan

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