Abstract:
The effects of
l-stepholidine(
l-SPD) on peripheral vascular dopamine DA
1 and DA
2receptors were studied using isolated vascular rings in rabbits. It was shown that (1)
l-SPD(0.1~10μmol·L
-1) shifted the dose-response curves to the right in a nonparallel fashion and decreased the maximal response (Emax) of both the fenoldopam(FODA,a selective DA
1 agonist)-induced and the propyl-buty-dopamine(PBDA, a selective DA
2 agonist)-induced vasorelaxation showing a non-competitive antagonistic action. The pD
2 values of
l-SPD for FODA in the renal, pulmonary and mesenteric arteries were 5.43, 5.48 and 5.58,respectively. The pD
2 values for PBDA in the mesenteric and femoral arteries were 5.35 and 5.89,respectively. The potencies of its antagonistic action were comparable to SCH23390, a selective DA
1 antagonist, and to domperidone, a selective DA
2 antagonist.(2)
l-SPD(0.1~100μmol·L
-1) per se was also found to induce slight but doserelated vasorelaxations in the renal and pulmonary arteries displaying its DA
1 agonistic activity.Its pD
2 values were 4.98 and 5.02, respectively. However, its Emax were considerably smaller than that of FODA. These results suggest that
l-SPD is a mixed peripheral DA
1 and DA
2receptor antagonists and weak DA
1 receptor agonist with pharmacological property of dual action.