Characterization of the adrenergic activity of arbutamine, a novel agent for pharmacological stress testing

ABSTRACT

Arbutamine is a novel catecholamine designed to be used as a diagnostic agent in patients with coronary artery diseases. The activity of this agent in anesthetized dogs was studied and its interactions with adrenoceptors in vitro were characterized. Arbutamine, 12.5, 25 and 50 ng/kg/min intravenous infusion, significantly increased the left ventricular pressure, cardiac output [CO], and the heart rate [HR]. It also reduced the total peripheral vascular resistance [TPVR]. These effects were compared to those produced by isoproterenol [ISO] and dobutamine [DOB] infused in doses of 3.75, 7.5 and 15 ng/kg/min and 2, 4 and 8 Ug/kg, respectively. The affinity constant [KA] of arbutamine and ISO for cardiac B1-adrenoceptors as determined by competition binding assays was found to be 7.32 and 6.04, respectively. In guinea pig trachea precontracted with histamine, arbutamine and ISO produced a concentration dependent relaxation. Arbutamine contracted isolated rate aortic rings with maximal activity that of norepinephrine [NE]. The interactions of arbutamine and ISO with the atypical B- adrenoceptors [B3] in rat white adipocytes, arbutamine simulated glycerol release were also studied. The order of potency of the agents tested is BRL-37344 > arbutamine > ISO; while in hamster brown adipocytes, the order is arbutamine > ISO > BRL-37344