α-Adrenoceptor blocking activity of fenoldopam (SK&F 82526), a selective DA1 agonist

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Abstract
The α-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 α-adrenoceptor antagonist, phenoxybenzamine, fenoldopam provided nearly complete protection against α-adrenoceptor blockade. These results demonstrate that fenoldopam possesses α-adrenoceptor antagonist activity and competes with α-phenoxybenzamine, for occupancy at the same receptor site.