Direct cardiac effects of a novel vesamicol receptor ligand, m-iodobenzyl-trozamicol assessed in the canine isolated, blood-perfused heart preparations

MIBT, m-(iodobenzyl)trozamicol, is a recently discovered vesamicol analogue that can be used as a functional marker of cholinergic activity in the hea rt as well as the brain. The purpose of this study was to assess the effect s of MIBT on sinus node automaticity, ventricular contraction, and coronary blood flow in addition to the action-potential duration of the ventricle b y using canine isolated, blood-perfused sinoatrial node and papillary muscl e preparations. Intracoronary administration of MIBT (1-300 mu g) exerted n egative chronotropic, inotropic, and coronary vasodilator effects in a dose -related manner. Pretreatment of the preparations with the muscarinic recep tor antagonist atropine did not change these effects of MIBT. Moreover, MIB T had little effect on the repolarization phase of the ventricular action p otential. Because the doses of MIBT needed for imaging cardiac cholinergic function were much lower than those affecting the cardiovascular system, MI BT may be used safely in future clinical applications.