Specificity of the serotonergic antagonist ketanserin.

Ketanserin reduces blood pressure effectively, but without inducing tachycardia. Its precise mode of action is unclear but under some circumstances it attenuates the rise in blood pressure caused by infusion of the alpha 1-agonist phenylephrine, suggesting that it acts at least partly as an alpha 1-adrenoceptor antagonist. However, the specificity of this attenuation has been questioned. We have therefore examined the effects of ketanserin on the blood pressure and heart rate responses to angiotensin II (a vasoconstrictor agent largely devoid of alpha 1-agonist properties). The blood pressure response to infused angiotensin II, in contrast to that of phenylephrine, was not attenuated by ketanserin. Ketanserin appeared not to increase cardiac efferent parasympathetic activity. At a dose used in the treatment of hypertension, ketanserin produces alpha 1-antagonism in man, which may partly explain its antihypertensive effect.