Antagonism towards endogenous adenosine and inhibition of cGI-PDE in the cardiac effects of amrinone, milrinone and related analogues.

Abstract 1. 1. The effect of amrinone, milrinone and of three milrinone analogues was tested on spontaneous chronotropic and inotropic activity of guinea-pig isolated atria, on the activity of cGMP-inhibited phosphodiesterase (cGI-PDE) from guinea-pig heart and on specific binding of N 6 -cyclohexyl[ 3 H]adenosine ([ 3 H]CHA) to R i adenosine receptors in guinea-pig atria. 2. 2. The K i -values towards [ 3 H]CHA binding to R i receptors were linearly related to the EC 50 s for the increase in force of contraction but not to the EC 50 s for the increase in frequency of the atria. The K i values towards cGI-PDE were linearly related to the EC 50 s for the positive chronotropic effect.