Cardiovascular responses in healthy subjects to a novel oral dopamine agonist, fenoldopam.
Two double-blind randomized crossover studies were carried out in healthy male subjects to determine the cardiovascular effects of fenoldopam and to assess whether they could be modified by metoclopramide. Blood pressure (BP) and heart rate (HR) were measured supine and upright, before and for up to 4 h after dosing. Single oral doses of fenoldopam 50, 100 or 150 mg or placebo were administered in one study. In the other study, subjects received 20 mg metoclopramide or placebo intravenously, 20 min before an oral dose of 100 mg fenoldopam or placebo. Fenoldopam produced decreases in diastolic BP and increases in HR indicative of an orally active systemic arteriolar vasodilator. Mean peak responses occurred 30-60 min after dosing and values had returned to pretreatment levels within 3-4 h. The decrease in diastolic BP was partially attenuated by pretreatment with metoclopramide. Thus, at least in part, the fall in BP following fenoldopam could be due to an interaction with dopamine receptors.
Cregeen
R J
RJ
Clinical Research Department, Smith Kline and French Research Ltd, Welwyn, Herts, UK.
Rudge
P J
PJ
Mills
J G
JG
Vincent
S H
SH
Burland
W L
WL
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology*; D004311:Double-Blind Method; D018818:Fenoldopam; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male
D015259:Dopamine Agents; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D018818:Fenoldopam