In vitro myocardial effects of 4-(3,4-dimethoxybenzyl)-2-imidazolidinone (Ro 7-2956).

The myocardial effects of 4-(3,4-dimethoxybenzyl)-2-imidazolidinone (Ro 7-2956), a phosphodiesterase inhibitor, were investigated utilizing in vitro preparations. The compound produced a positive chronotropic effect in spontaneously beating guinea-pig atria which was not blocked by propranolol. It also produced an upward shift of the frequency-force curve obtained in stimulated left atria of guinea pigs, resembling that due to elevated [Ca ++ ]. The cumulative log dose-response curve for Ca ++ in stimulated atria was shifted to the left by Ro 7-2956. The compound prolonged the time course of tension decline in atria exposed to Ca ++ -free medium. Ro 7-2956 and elevated [Ca ++ ] produced similar effects on active tension development in cat papillary muscles; however, Ro 7-2956 produced a significantly greater increase in the rate of tension development, produced a greater shortening of the time to peak tension and decreased the total duration of the contraction.