Effects of AR-L 115 BS, a new cardiotonic compound, on cardiac contractility, heart rate and blood pressure in anaesthetized and conscious animals.

In anaesthetized dogs, 0.03--10 mg/kg 2-[(2-methoxy-4-methylsulfinyl)-phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS) i.V. increased dp/dtmax by 3-221% and VCE by 1-196%. Threshold doses for a positive chronotropic effect were higher, beginning at 0.3 mg/kg and amounting to +70% at 10 mg/kg. Systemic blood pressure was not influenced significantly, whereas pulmonary pressure was lowered slightly at all doses and likewise left ventricular enddiastolic pressure at 3 and 10 mg/kg. Similar effects were observed in anaesthetized baboons at 0.1--5 mg/kg and in mini-pigs at 0.1--10 mg/kg i.v. Duration of the effect on contractility parameters was 20 to 100 min depending on dose. In conscious dogs with telemetric measurement of left ventricular pressure, dp/dt and heart rate, 2.5--30 mg/kg AR-L 115 BS orally augmented dp/dtmax by 16-92% for 5 to 12 h. Systolic blood pressure and heart rate were modestly increased. The investigation of the basal values of cardiac contractility and the efficacy of i.v. administered AR-L 115 BS in dogs pretreated with 10 mg/kg/day orally for 6 and 12 months indicated that the compound did not accumulate and that no tolerance to the drug developed.