piperidines and bucindolol

Bucindolol is a new beta-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. Bucindolol 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 alpha-adrenergic antagonist properties in addition to its documented beta-adrenoceptor antagonist properties. This appears to be a novel combination of antagonist properties. Bucindolol also reduced the maximal response to 5-HT but had no effect on the maximal response to PE. In these respects, bucindolol acts similarly to prazosin (alpha-adrenoceptor blocker) and ketanserin (5-HT antagonist and alpha-adrenoceptor blocker). These results are consistent with our proposal that 5-HT receptors and alpha-adrenoceptors overlap on the cell surface, sharing common binding sites, such that alpha-adrenoceptor blockade causes interference with the full expression of 5-HT receptor stimulation.

Topics: Adrenergic alpha-Antagonists; Animals; Blood Pressure; In Vitro Techniques; Ketanserin; Male; Phenylephrine; Piperidines; Prazosin; Propanolamines; Rats; Rats, Inbred Strains; Regional Blood Flow; Serotonin Antagonists