Bucindolol Has Serotonin and α-Adrenoceptor Blocking Properties

Bucindolol is a new β-adrenoceptor antagonist that lowers blood pressure partly via direct vasodilation. We have investigated the mechanism of the antihypertensive action of bucindolol using the isolated perfused rat tail artery preparation. Bueindolol caused a parallel shift to the right of the dose-response curves for both serotonin (5-HT) and phenylephrine (PE), indicating competitive antagonism. The pA2 values were 5.9 ± 0.2 (5-HT) and 7.18 + 0.10 (PE). The calculated potency ratio (PE:5-HT) was 19. Thus, bucindolol was found to have weak serotonin antagonist as well as α-adrenergic antagonist properties in addition to its documented β-adrenoceptor antagonist properties. This appears to he a novel combination of antagonist properties. Bucindolol also reduced the maximal response to 5-HT hut had no effect on the maximal response to PE. In these respects. bueindolol acts similarly to prazosin (α-adrenoceptor blocker) and ketanserin (5-HT antagonist and α-adrenoceptor blocker) These results are consistent with our proposal that 5-HT receptors and α-adrenoceptors overlap on the cell surface. sharing common binding sites, such that α-adrenoceptor blockade causes interference with the full expression of 5-HT receptor stimulation.