Positive inotropic action and conformation difference of lupin alkaloids in isolated cardiac muscle of guinea pig and bullfrog

The cardiac effects of the lupin alkaloids, matrine (Mat), allomatrine (Amat), oxymatrine (Omat), sophoridine (Sori) and sophoramine (Sora) were compared in guinea‐pig papillary muscle stimulated electrically and in isolated perfused bullfrog heart. Mat (0.4–2.4 mM), Amat (0.41–6.5 mM), Sori (0.68–6.3 mM) and Sora (0.61–6.5 mM) possessed positive inotropic effects, but not Omat (4.84 mM). The relative intrinsic activity was Amat>Mat>Sora>Sori. The effects of lupin alkaloids on isoproterenol (Isp)‐or Ca 2+ ‐induced contraction were also tested in guinea‐pig papillary muscle. Mat, Amat, Sori and Sora, but not Omat, at a concentration (0.4 mM) inducing less or no inotropic effect, shifted the concentration‐response curves for Isp to the left and/or upward, and the maximal response of the concentration‐response curve for Ca 2+ was only increased by Sora and Mat. The cardiotonic effects of lupin alkaloids were composed of: (1) potentiation of isoproterenol‐induced positive inotropic effects at low concentrations; and (2) a direct positive inotropic action at high concentrations. As the lupin alkaloids have similar chemical structures but different steric configurations, their patterns of cardiotonic actions were clearly different.