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

In this study, we characterized the interactions of arbutamine, a novel catecholamine developed for use as a cardiac stress testing agent, with different adrenergic receptor subtypes in vitro. These effects were compared with those of isoproterenol. In the electrically stimulated left atria of rats, arbutamine increased contractile force. The pD2 values (- log of the dose that produces 50% of the maximal responses) for arbutamine and isoproterenol were 8.45 +/- 0.15 and 8.55 +/- 0.02, respectively. Metoprolol shifted the concentration-effect curves for both isoproterenol and arbutamine to the right with a pA2 value (- log of the dose of the antagonist that reduces the maximal responses of an agonist to 50%) of 7.22-7.5. Both arbutamine and isoproterenol increased the rate of spontaneously beating rat right atria with pD2 values of 9.0 +/- 0.19 and 8.82 +/- 0.18, respectively. The affinity constants (KA) of arbutamine and isoproterenol for cardiac beta1-adrenergic receptors, as determined by competition binding assays, were found to be 7.32 and 6.04, respectively. In guinea pig trachea, arbutamine and isoproterenol produced a concentration-dependent relaxation that was blocked by propranolol. Their pD2 values were 7.9 +/- 0.1 and 8.2 +/- 0.1, respectively. Arbutamine contracted isolated rat aortic rings with a maximal increase of 38.1 +/- 6.7% that of 10 microM of norepinephrine. In rat white adipocytes, arbutamine, isoproterenol, and BRL-37344 stimulated glycerol release, with the order of potency being BRL-37344 > arbutamine > isoproterenol. In hamster brown adipocytes, the order was arbutamine > isoproterenol > BRL-37344. Moreover, arbutamine stimulated beta3-adrenergic receptors in guinea pig ileum. In conclusion, arbutamine is a novel catecholamine with similar potency and efficacy to that of isoproterenol. It stimulates cardiac beta1-, tracheal beta2-, and adiopocyte beta3-adrenergic receptors. Arbutamine does not stimulate alpha-adrenergic receptors at concentrations that were high enough to maximally activate the beta-adrenergic receptors.