High selectivity for inhibition of phosphodiesterase III and positive inotropic effects of MCI-154 in guinea pig myocardium.

MCI-154 (0.3-100 μM) exerted a concentration-dependent positive inotropic effect in isolated guinea pig papillary muscles (EC 50 0.8 μM). The efficacy of MCI-154 (253% of predrug value) was 1.7-fold higher than that of saterinone but comparable to that of milrinone. Carbachol markedly reduced the increase in force of contraction (FOC) of MCI-154. In intact contracting papillary muscles, the positive inotropic effect was accompanied by an increase in cyclicAMP content to 0.78±0.09 pmol/mg wet weight (n=10), corresponding to 150% of the basal value (0.51±0.05 pmol/mg wet weight, n=21) in the presence of submaximal cyclicAMP phosphodiesterase (PDE) isoenzyme III inhibiting concentrations of MCI-154 (30 μM)