The dopamine receptor agonist Z1046 reduces ischaemia severity in a canine model of coronary artery occlusion

Abstract Z1046, ( S )-6[[6-[[2-(2-methoxyphenoxy)ethyl]amino]propyl]amino]-5,6,7,8-tetra-hydro-1,2-naphtalenediol dihydrochloride, is an agonist at both dopamine D 1 and D 2 receptors. Since stimulation of dopamine D 2 receptors inhibits noradrenaline release, and because cardiac noradrenaline release has been implicated in the genesis of early ischaemia-induced, life-threatening ventricular arrhythmias, the effect of Z1046 has been examined for its effects on coronary artery occlusion in chloralose–urethane anaesthetised mongrel dogs. Z1046 (10 μ g kg −1 intravenously or 1 μ g kg −1 by local intracoronary injection) decreased heart rate and reduced arterial blood pressure and coronary blood flow, effects prevented by the prior administration of domperidone (40 μ g kg −1 i.v.). The ischaemic changes induced by a 25-min occlusion of the left anterior descending coronary artery (including ST-segment elevation and ventricular ectopic activity) were much less marked in those dogs administered Z1046 and survival from the combined ischaemia–reperfusion insult was increased from 7% to 36% ( P