Propylbutyldopamine: hemodynamic effects in conscious dogs, normal human volunteers and patients with heart failure.

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Abstract
The cardiovascular actions of a dopamine analog, propylbutyldopamine (PBDA), were examined for the first time in conscious dogs, normal human volunteers and patients with congestive heart failure. PBDA lowered blood pressure without reflex increases in heart rate, increased renal blood flow and decreased renal vascular resistance in dogs previously instrumented to allow measurement of arterial pressure and regional vascular flows in the conscious, unrestrained state. Pretreatment of the dogs with (S)-sulpiride, an antagonist selective for the dopamine receptor located on noradrenergic neurons (DA2), attenuated the reduction in arterial pressure but not the increase in renal blood flow produced by PBDA at a dose of 20 .mu.g/kg per min. The emetic potency of this dopamine analog was examined in conscious dogs; the drug caused vomiting on 2 of 22 occasions at an i.v. infusion rate of 20 .mu.g/kg per min and on 6 of 11 occasions at a dosage of 40 .mu.g/kg per min. In contrast to its effects in conscious dogs, PBDA in nonemetic dosages (20-40 .mu.g/kg per min) failed to lower blood pressure in 3 normal volunteers but slightly increased heart rate and doubled renal blood flow as measured by changes in the clearance of p-aminohippurate. Pretreatment of the volunteers with metoclopramide, 20 mg i.v., antagonized the increase in both heart rate and renal blood flow produced by PBDA. In 11 patients with congestive heart failure not due to valvular or congenital heart disease, i.v. infusion of PBDA at 5, 10 and 20 .mu.g/kg per min resulted in dose-dependent reductions in mean arterial pressure, left ventricular filling pressure and pulmonary and systemic vascular resistances, and increases in cardiac index, without changes in stroke work index or heart rate. The demonstration that PBDA decreases systemic vascular resistance and blood pressure in patients with heart failure and increases renal blood flow in dogs and normal volunteers introduces a new class of drugs with unique mechanisms of action and advantages for the treatment of conditions such as congestive heart failure and hypertension. The possibility that this drug class acts through activation of peripheral DA2 presynaptic and DA1 postsynaptic dopamine receptors appears strong and further studies with this and similar agonists should stimulate the study of DA2 receptors in man.