[The effect of AR-L 115 BS on the function and oxygen consumption of isolated guinea pig atria as compared to g-strophanthin and theophylline]

Abstract

Dose-response curves with ouabain, theophylline and 2-[(2-methoxy-4- methylsulfinyl)phenyl] -1H-imidazo[4,5-b]pyridine (AR-L 115 BS) were obtained from electrically driven isolated left guinea pig atria (at 35 degrees C and 3 Hz, 0.5 ms and 0.4--0.6 mA 10% above threshold) measuring the auxotonic contraction work beat. The dose-response curve of the inotropy and frequency was very similar in shape to that of theophylline as far as intensity of inotropy and the range of dosage is concerned, but AR-L 115 BS is 10 times as active. The maximum of the increase of frequency was less under AR-L 115 BS than under theophylline. Also the toxicities of the two substances are very similar with a concomitant decline of inotropism. Both substances are clearly distinct from ouabain. As to the economic effect, however, AR-L 115 BS shows, in submaximally effective concentrations, similarity to the economic type of ouabain whereas, at the maximum of contractile activity, the efficiency is lowered as was observed with theophylline. In the "anoxia test" the anoxic tolerance was shortened by AR-L 115 BS similar to theophylline when the anoxic contractile activity was stimulated below the maximum level in contrast to the prolongation due to ouabain.