The cardiovascular effects of trimazosin and prazosin in the rabbit.

The cardiovascular effects of trimazosin, a quinazoline derivative similar in structure to prazosin, were investigated and compared with prazosin in the rabbit. Radioligand binding to cerebral membranes showed that trimazosin has roughly 100-fold less affinity for the alpha 1-adrenoceptor. This was further supported by its lower pA2 derived from phenylephrine contractile responses in isolated thoracic aorta preparations. Trimazosin is less extensively distributed and has a lower clearance from whole blood than prazosin although their whole blood elimination half-lives are comparable. In addition, although it is a less potent alpha 1-adrenoceptor antagonist in vivo, its peripheral vascular depressor effect tends to be greater than prazosin. Trimazosin at the dose used and under the conditions of study did not reverse the peripheral pressor effect of angiotensin II or B-HT920 but at higher concentrations, unlike prazosin, it relaxed the K+ contracted thoracic aorta. In addition, following pharmacological autonomic blockade and treatment with prazosin in vivo, trimazosin caused a further depressor response. A similar though shorter lasting non-alpha 1-receptor mediated action was also observed with prazosin. 1-Hydroxytrimazosin (CP23445), the major metabolite of trimazosin in man, showed little affinity for either the alpha 1- or alpha 2-adrenoceptor from radioligand binding studies. In addition to alpha 1-adrenoceptor antagonism, trimazosin may exert an additional direct vasodilator effect in rabbits.