alpha-Adrenoceptor blocking properties of a new antihypertensive agent, 2-[4-(n-butyryl)-homopiperazine-1-yl]-4-amino-6,7-dimethoxyquinazoline (E-643).
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 adrenaline dose-dependently and an adrenaline-reversal was seen with large doses. The in vivo alpha-adrenoreceptor blocking effect of E-643 was 3.4 times more potent than that of phentolamine. On the other hand, hypotensive action of E-643 was 9.4 times more potent than that of phentolamine. In the isolated rabbit aorta, E-643 blocked noradrenaline-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+. These data suggest that E-643 is a specific and competitive inhibitor of noradrenaline at the alpha-adrenoceptors.
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001464:Barium / Q000037:antagonists & inhibitors; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000037:antagonists & inhibitors; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011188:Potassium / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D011799:Quinazolines; D010643:Phenoxybenzamine; D001464:Barium; C018176:bunazosin; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine