Potent α-adrenoceptor blocking action of SGB-1534, a new quinazoline antihypertensive agent In vitro experiments

Characterization of a novel .ALPHA.1-adrenoceptor antagonist, SGB-1534, in contractile response of isolated canine arterial and venous smooth muscle to exogenous noradrenaline: Comparison with prazosin, phentolamine and yohimbine.

“…Phentolamine nonselectively blocks both a, and a2-adrenoceptors. SGB-1534, like prazosin (8,19), is a selective antagonist at a,-adrenoceptors (10)(11)(12)(13)(14). it is not surprising that in the present experiment, SGB-1534 as well as prazosin caused a nonparallel shift to the right of the concentration-response curve to nor adrenaline in the canine venous smooth muscles, since the presence of two subtypes of a-adrenoceptors was predicted particularly in the venous smooth muscle.…”

“…SGB-1 534 is a novel anti hypertenSIVE drug currently undergoing clinical evaluatior (9). Recently, it has been revealed that SGB 1534 possesses a selective a, -adrenoceptor antagonistic activity in in vitro and in vivc preparations from guinea pigs and rats (10), rabbits and cats (11), and dogs (12). Fur thermore, Nagatomo et al (13) and Aono and Sakai (14) using dogs and rats, respec tively, found in recent 3H-radioligand experi ments that SGB-1534 binds with a highly specific affinity, comparable to that of prazosin, to a, -adrenoceptor sites in the brain and the aorta, but not to a2-adrenoceptor sites.…”

Investigations into the Mechanism of the Antihypertensive Effect of SGB-1534, a Novel α1-Adrenoceptor Antagonist, in Rats

“…SGB-1534 is a novel antihypertensive drug (5) currently undergoing clinical evaluation. A series of these experiments have revealed that the mechanism by which SGB-1534 lowers blood pressure is greatly dependent on interruption of the sympathetic nervous system via peripheral a, -adrenoceptor blockade (6)(7)(8)(9). However, there are no precise investigations pertaining to the participation of any central component in the hypotensive effect of SGB-1 534.…”

Comparison of Cardiovascular Effects of SGB-1534 and Prazosin, Selective α1-Adrenoceptor Antagonists, in Anesthetized Dogs

“…SG B-1534 produced dose dependent decreases in systemic (systolic, mean and diastolic) blood pressure (SBP), SGB-1534, a novel phenylpiperazine derivative, is an orally active, long-lasting anti hypertensive agent which effectively lowered blood pressure in several hyper tensive rat models (1). Recently, it has been demonstrated that SGB-1 534 possesses a selective a,-adrenoceptor blocking activity in in vitro and in vivo preparations of guinea pigs and rats (2), rabbits and cats (3), and dogs (4). Furthermore, Nagatomo et al (5) found n recent 3H-radioligand experiments that SGB-1534 binds with a highly specific affinity, comparable to that of prazosin, to ai -adrenoceptor sites in the brain and the aorta of the dog, but not to a2-adrenoceptor sites.…”