.ALPHA.-Adrenoceptor blocking properties of a new antihypertensive agent,2-(4-(n-butyryl)-homopiperazine-1-yl)-4-amino-6,7-dimethoxyquinazoline (E-643).

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Abstract
Postsynaptic .alpha.-receptor blocking properties of E-643 were studied in vivo and in vitro and compared with these same properties of phentolamine and phenoxybenzamine. In anesthetized rats E-643 (i.v.) attenuated pressor response to adrenalin [epinephrine] dose-dependently and an adrenalin-reversal was seen with large doses. The in vivo .alpha.-adrenoceptor blocking effect of E-643 was 3.4 times more potent than that of phentolamine. Hypotensive action of E-643 was 9.4 times more potent than that of phentolamine. In the isolated rabbit aorta E-643 blocked noradrenalin[norepinephrine]-induced contraction of the aorta with a parallel shift of the dose-response curve to the right. The pA2 values for E-643 and phentolamine were 8.60 and 7.65, respectively. The .alpha.-blocking effect of E-643 was reversible. E-643 protected .alpha.-receptors against irreversible inhibition by phenoxybenzamine. E-643 neither exhibited significant blocking effects on K+-, Ba2+- and angiotensin-induced contractions of the aorta nor caused relaxation of the aorta contracted by Ca2+. E-643 apparently is a specific and competitive inhibitor of noradrenalin at the .alpha.-adrenoceptors.