POSITIVE INOTROPIC AND VASOCONSTRICTOR RESPONSES TO 14β-AMINOPREGNANE DERIVATIVES IN ISOLATED TISSUES FROM THE GUINEA-PIG

1. The objective of this study was to compare the positive inotropic and vasoconstrictor responses in guinea-pig isolated tissues of the aminosteroid derivatives LND 623 and LND 796 and the cardiac glycoside ouabain. 2. Ouabain (-log EC50, 6.66 +/- 0.04, n = 11) was more potent as a positive inotropic agent on guinea-pig right ventricular papillary muscles than either LND 623 (-log EC50, 6.26 +/- 0.08, n = 6) or LND 796 (-log EC50 5.66 +/- 0.05, n = 7). All compounds gave similar maximal increases in force of contraction. However, the ratio of the maximally effective concentration to the concentration giving 25% of the maximal response was approximately doubled for the aminosteroids compared with ouabain. 3. Ouabain (-log EC50 6.27), LND 623 (-log EC50 6.24) and LND 796 (-log EC50 5.43) produced slowly developing contractions of guinea-pig thoracic aortic rings. 4. These results indicate that, while the aminopregnane derivatives and ouabain produce qualitatively similar results, the therapeutic range for the positive inotropic responses is greater for the aminosteroids.