Hemodynamic effects of an oral dopamine receptor agonist (fenoldopam) in patients with congestive heart failure

Dopamine receptor stimulation causes vascular and neurohumoral responses that may be beneficial in patients with heart failure. Oral inactivity, emesis and adrenergic-induced arrhythmias have limited the use of currently available compounds. Fenoldopam (SKF-82526-J) is a new, orally available, selective, dopamine-receptor agonist with potent renal vasodilating properties (six times that of dopamine) without positive inotropic or adrenergic activity. Drug efficacy was clinically evaluated in 10 patients with heart failure after single oral doses of placebo and 50, 100 and 200 mg of medication. Placebo produced no changes. Peak efficacy was noted 30 minutes to 1 hour after the 200 mg dose with mean blood pressure decreasing from 96 ± 15 (mean ± SD) to 83 ± 8 mm Hg (p < 0.05), pulmonary capillary wedge pressure decreasing from 23 ± 6 to 20 ± 8 mm Hg (p < 0.05) and mean pulmonary artery pressure decreasing from 32 ± 9 to 29 ± 8 mm Hg (p < 0.05). Systemic vascular resistance decreased from 1,987 887 to 1,191 ± 559 dynes-s-cm^-5 (p < 0.05) with a subsequent 55% increase in cardiac index from 2.2 ± 1.1 to 3.1 ± 1.3 liters/min per mZ (p < 0.05). Heart rate and right atrial pressure did not change (p>0.05). No emesis or new tachycardia was noted at any dose. Basefine hemodynamics generally returned within 3 to 4 hours. Fenoldopam, therefore, is a short-acting, orally effective drug that decreases systemic vascular resistance and increases cardiac index in patients with heart failure and represents a new class of oral compounds that may be useful in treating such patients.