Analysis of the positive-inotropic activity of the benzimidazole derivative AR-L 115 BS in isolated guinea pig atria.

When comparing the positive-inotropic effect of 2-[(2-methoxy-4-methylsulfinyl)phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS) on the isolated guinea pig atria with those of theophylline, orciprenaline and strophanthin G, the following results were obtained: 1. In left atria the maximum effective concentration of AR-L 115 BS is 3.16 x 10(-4), of theophylline 10(-3), of strophanthin G 6.81 x 10(-7) and of orciprenaline 10(-5) mol/l. The increase in the contractile force thereby obtained was 192, 111, 158 and 277%, respectively (extracellular calcium concentration 1.2 mmol/l). Therefore AR-L 115 BS is somewhat less effective than orciprenaline but more effective than theophylline and strophanthin G. 2. AR-L 115 BS is also effective in atria isolated from animals pretreated with reserpine and its effect is not reduced in the presence of bupranolol. 3. Contrary to strophanthin G, AR-L 115 BS has a shorter time of onset of activity and is less dependent on the extracellular calcium concentration. 4. Similar to theophylline, AR-L 115 BS inhibits the positive-inotropic effect of orciprenaline dose-dependently, while strophanthin G increases the positive-inotropic effect of orciprenaline. 5. The effect of AR-L 115 BS differs from that of orciprenaline in having only little effect on the contraction rate in isolated right atrial preparations.