Effects of a novel vesamicol receptor ligand, m-(iodobenzyl)trozamicol, on the canine isolated, blood-perfused atrioventricular node preparation.

m-(Iodobenzyl)trozamicol (MIBT) is a recently discovered vesamicol analogue. It has been shown that radiolabelled [125I]MIBT can be used as a marker of cholinergic innervation in the heart as well as in the brain. The purpose of this study was to analyze the direct effects of MIBT on the atrioventricular and intraventricular conduction in addition to the coronary blood flow using the canine isolated, blood-perfused atrioventricular node preparation. Intracoronary administration of MIBT suppressed the atrioventricular and intraventricular conduction, while it increased the coronary blood flow. The effect and duration of action on the intraventricular conduction was less pronounced compared with other effects. Moreover, the doses of MIBT needed to cause negative dromotropic and coronary vasodilator effects in this study was much greater than those needed for imaging the cardiac cholinergic innervation. Pretreatment of the preparations with a muscarinic receptor antagonist, atropine, did not block these effects of MIBT, suggesting that MIBT may possess muscarinic receptor-independent ion channel activity in the cardiac conduction system and coronary arteries.