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Effect of YM-12617, a selective and potent alpha 1-adrenoceptor antagonist on dose-response curves of alpha 1-adrenoceptor agonists, norepinephrine, phenylephrine and naphazoline, was tested in isolated rabbit vascular smooth muscles such as the femoral vein, portal vein and aorta. YM-12617 shifted the dose-response curves for norepinephrine and phenylephrine to the right and also declined the maximum response in the femoral vein, where norepinephrine and phenylephrine behaved as low efficacy agonists. Similar results were obtained on the curve of naphazoline in the portal vein, where the efficacy of naphazoline was low. However, the efficacies of norepinephrine, phenylephrine and naphazoline were high in the aorta. The dose-response curves for three alpha 1-agonists were shifted by YM-12617 in a parallel manner in the aorta. The curves of norepinephrine and phenylephrine were also shifted by YM-12617 in the portal vein, where the efficacies of both the alpha 1-agonists were high. The present results suggest that the mode of antagonism between the alpha 1-agonist and alpha 1-antagonist is dependent on the efficacy of the alpha 1-agonist which depends upon the receptor-density in the organ used.

Difference in Mode of Action of Alpha1-Adrenoceptor Antagonists on Some Vascular Smooth Muscles and Efficacy