Alpha-adrenoceptor blocking activity of fenoldopam (SK&F 82526), a selective DA1 agonist.
The alpha-adrenoceptor blocking activity of fenoldopam (SK&F 82526), a selective dopamine vascular receptor (DA1) agonist, was evaluated in isolated segmental preparations of rabbit aorta, dog mesenteric and rabbit splenic arteries. Fenoldopam, in concentrations ranging from 10(-6) to 10(-4) M, produced parallel, dextral shifts of concentration-contractile response curves to noradrenaline. Slopes of the Schild regression lines were not significantly different from unity in the three vessels. pA2 values for fenoldopam in the rabbit aorta, dog mesenteric and rabbit splenic arteries were 5.48 +/- 0.08, 5.78 +/- 0.05, and 5.20 +/- 0.05, respectively. In experiments where the drug was added to the bathing medium before exposing the vascular segments to the irreversible alpha-adrenoceptor antagonist, phenoxybenzamine, fenoldopam provided nearly complete protection against alpha-adrenoceptor blockade. These results demonstrate that fenoldopam possesses alpha-adrenoceptor antagonist activity and competes with alpha-phenoxybenzamine, for occupancy at the same receptor site.
Nakamura
S
S
Kohli
J D
JD
Rajfer
S I
SI
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology*; D015237:Dinoprost; D004285:Dogs; D005260:Female; D018818:Fenoldopam; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D010643:Phenoxybenzamine / Q000037:antagonists & inhibitors; D011189:Potassium Chloride / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D011817:Rabbits; D013157:Splenic Artery / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D001552:Benzazepines; D011460:Prostaglandins F; D010643:Phenoxybenzamine; D011189:Potassium Chloride; D015237:Dinoprost; D018818:Fenoldopam; D009638:Norepinephrine