Abstract
Arbutamine, 1,2‐Benzenediol,4‐[1‐hydroxy‐2‐[[4‐(4‐hydroxyphenyl)butyl[amino]ethyl]rsqb;rsqb; hydrochloride, (R), is a new catecholamine being developed as a pharmacologic stress agent for the diagnosis of coronary artery disease and myocardial ischemia. The pharmacology of arbutamine was studied in vitro using receptor binding assays and functional bioassays of α‐ and β‐adrenoceptor activity, and in vivo using the hemodynamic responses to intravenous infusion in anesthetized and conscious dogs. In isolated membranes, receptor binding studies demonstrated K~i~ values of 196 ± 12 nM and 147 ± 11 nM for β~1~‐ and β~2~‐adrenoceptors, and 265 ± 4 nM and 867 ± 40 nM for α~1~‐ and β~2~‐adrenoceptors, suggesting that arbutamine is a mixed β~1+2~‐adrenoceptor agonist with significant affinity for β~1~‐adrenoceptors. This was supported by in vitro bioassay data, where arbutamine increased spontaneous atrial rate (β~1~‐activity, ED~50~ = 16 ± 6 nM), relaxed isolated tracheal rings (β~2~‐activity, ED~50~ = 13 ± 5 nM), and contracted aortic rings (α‐activity, ED~50~ = 430 ± 80 nM), indicating 25–30‐fold selectivity for β‐adrenoceptor activation. In conscious or anethetized dogs, arbutamine elicited dose‐dependent increases in heart rate and LV dP/dt with little fall in mean arterial pressure. The data demonstrate that arbutamine exhibits similar degrees of intropic and chronotropic activity, while eliciting less peripheral vasodialation than isoproteronal and less inotropic activity than dobutamine. Moreover, there was rapid termination of the tachycardia, as heart rate resolved to 50% of the maximal effect within 7.2 ± 1.1 min following arbutamine, compared to 5.5 ± 1.0 min following isoproterenol and 5.9 ± 1.4 min following dobutamine. This hemodynamic profile and rapid pharmacodynamic offset makes arbutamine ideally suited for use as a pharmacologic stress agent.