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 heart as well as the brain. The purpose of this study was to assess the effects of MIBT on sinus node automaticity, ventricular contraction, and coronary blood flow in addition to the action-potential duration of the ventricle by using canine isolated, blood-perfused sinoatrial node and papillary muscle preparations. Intracoronary administration of MIBT (1-300 microg) exerted negative chronotropic, inotropic, and coronary vasodilator effects in a dose-related manner. Pretreatment of the preparations with the muscarinic receptor antagonist atropine did not change these effects of MIBT. Moreover, MIBT had little effect on the repolarization phase of the ventricular action potential. Because the doses of MIBT needed for imaging cardiac cholinergic function were much lower than those affecting the cardiovascular system, MIBT may be used safely in future clinical applications.
Sugiyama
A
A
Department of Pharmacology, Yamanashi Medical University, Nakakoma-gun, Japan. atsushis@res.yamanashi-med.ac.jp
Lurie
K G
KG
Efange
S M
SM
Takehana
S
S
Hashimoto
K
K
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007462:Iodobenzenes / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D010477:Perfusion; D010880:Piperidines / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000187:drug effects*; D012849:Sinoatrial Node / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D007462:Iodobenzenes; D008024:Ligands; D010880:Piperidines; D011950:Receptors, Cholinergic; C083232:vesamicol receptor; C081671:(3-iodobenzyl)trozamicol