Sympathomimetic amines having a carbostyril nucleus

Abstract

A series of new sympathomimetic amines containing an 8-hydroxycarbostyril moiety was synthesized. These compounds probably exist as resonance hybrids having two acidic hydrogen atoms in locations approximating to those of the hydroxyl groups of catechol-containing adrenergic agents. In an in vitro test, many of these compounds showed potent activity for relaxation of guinea pig tracheal smooth muscle. One of the compounds was 24 000 times more potent than isoproterenol. Their actions on cardiac muscle were also examined in vitro by measuring increase in the beating rate of the right atria of guinea pigs. Several of the compounds appeared to be beta-selective. Some of the compounds seem suitable for use as bronchodilators. The structure-activity relationships of these compounds were discussed in comparison with those of catecholamines.

Pre‐ and post‐junctional actions of procaterol, a β2‐adrenoceptor stimulant, on dog tracheal tissue

“…The Kd values of ICI-118551 against #2-adrenoceptor measured in guinea-pig trachea, bronchi and parenchyma ranged between 10-9-7 x 10-0M (Carswell & Nakorski, 1983). well-documented direct actions on the airway smooth muscle cells (Yoshizaki et al, 1976;Yabuuchi et al, 1977;Himori & Taira, 1977;Tei et al, 1979;Yamashita et al, 1987;Fujiwara et al, 1988). Low concentrations of procaterol (10-1 10-9M) significantly suppressed the amplitude of e.j.p.…”

The Β‐ADRENOCEPTOR STIMULANT PROPERTIES OF OPC‐2009 ON GUINEA‐PIG ISOLATED TRACHEAL, RIGHT ATRIAL AND LEFT ATRIAL PREPARATIONS

“…Recently, Yoshizaki, Tanimura, Tamada, Yabuuchi & Nakagawa (1976) reported on a novel series of sympathomimetic amines having a carbostyril nucleus. One member of this series, 5-(l-hydroxy-2-isopropylaminobutyl)-8-hydroxycarbostyril hydrochloride hemihydrate (OPC-2009) (Figure 1) was selected for more detailed pharmacological study, for the preliminary experiments in vivo showed it to be a promising compound.…”

Agonist-induced desensitization of beta-adrenoceptor function in humans. Subtype-selective reduction in beta 1- or beta 2-adrenoceptor-mediated physiological effects by xamoterol or procaterol.

“…Procaterol treatment increased heart rate by [10][11][12][13][14][15] beats/min after 12-24 hours. During further treatment, heart rate declined slowly and reached predrug levels about 2-3 days after withdrawal of procaterol.…”