Selective and full β 1 ‐adrenoceptor agonist action of a catechol derivative of denopamine (T‐0509) in the guinea‐pig cardiac muscle and trachea: comparison with denopamine, xamoterol and isoprenaline

1 The pharmacological actions of T‐0509, a 3‐hydroxy derivative of denopamine, were studied in various guinea‐pig tissues; these effects were compared with those of isoprenaline, denopamine and xamoterol. 2 The intrinsic activities of the positive inotropic actions of T‐0509, denopamine and xamoterol compared with isoprenaline (= 100%) in the papillary muscle were 99%, 83% and 28%, respectively, while their relative potencies (EC 50 agonist EC 50 isoprenaline) were 0.23, 33 and 1.4, respectively. The intrinsic activities of T‐0509, denopamine and xamoterol as positive chronotropic agents in the right atria were 98%, 69% and 48%, respectively, and their equipotent concentrations (isoprenaline = 1) were 0.24, 50 and 4, respectively. 3 The positive chronotropic actions of T‐0509 and denopamine were antagonized by bisoprolol (3 × 10 −8 m ), but not by ICI 118,551 (3 × 10 −8 m ). 4 The intrinsic activity of T‐0509 in histamine‐contracted tracheae was similar to that of isoprenaline, but its equipotent concentration was 38; the effects of both agents were antagonized by ICI 118,551 (3 × 10 −8 m ), but not by bisoprolol (3 × 10 −8 m ). Denopamine and xamoterol did not show any agonist activity on guinea‐pig trachea. 5 Denopamine and xamoterol antagonized the positive chronotropic (pA 2 , denopamine: 6.98, xamoterol: 7.75) and tracheal relaxant (pA 2 , denopamine: 5.39, xamoterol: 6.25) effects of isoprenaline. 6 Isoprenaline, T‐0509 and denopamine, but not xamoterol, contracted the guinea‐pig aorta in a decreasing order in the presence of propranolol (10 −6 m ). 7 Based on the above studies, T‐0509 appears to be a highly selective β 1 ‐adrenoceptor agonist with full agonist properties, while denopamine and xamoterol appear to be selective, but partial ft ‐adrenoceptor agonists.