Hemodynamic effects of Corwin (ICI 118,587), a new cardioselective beta-adenoceptor partial agonist

To describe the mechanisms of action of Corwin (ICI 118,587), a new cardioselective beta-adrenoceptor partial agonist, ten cardiac patients with mild to moderate functional cardiac impairment were studied. Hemodynamic measurements were made at rest and during three consecutive levels of submaximal exercise, before and 10 min after intravenous administration of 0.2 mg/kg of the drug. At rest, Corwin increased heart rate (HR) from 75 to 88 bpm and mean systemic blood pressure (BP) and decreased mean pulmonary capillary wedge pressure (PCWP); the resting cardiac output (CO) tended to increase in patients with a slow control HR. During exercise of low intensity (control HR: 103 bpm), the drug had no significant effect, except for a slight decrease in BP. During exercise of moderate and heavy intensity (control HR: 121 and 149 bpm), Corwin decreased HR (-10 and -24 bpm), BP and PCWP; at the heaviest exercise level, CO also decreased after Corwin. Thus, at rest, when the sympathetic tone is low, Corwin acts mainly as a beta-adrenoceptor agonist. As the sympathetic tone progressively increases with the intensity of the exercise, the beta-adrenoceptor antagonist action of Corwin becomes apparent and is most evident at the highest exercise level. In contrast to a full antagonist, these effects of Corwin appear to be less marked and they are accompanied by an unchanged or decreased PCWP. Corwin has thus interesting hemodynamic properties which deserve further investigation.