Antiarrhythmic agent amiodarone possesses calcium channel blocker properties.
Amiodarone possesses multiple pharmacologic properties, including peripheral and coronary vasodilatation, negative inotropy, and negative chronotropic and dromotropic effects. These properties are shared by the group of drugs termed calcium channel blockers. We examined the interaction of amiodarone with receptors for the 1,4-dihydropyridine (DHP) calcium blockers in rat and rabbit myocardial membrane particulates. Amiodarone displaced specifically bound [3H]nitrendipine in both rat and rabbit preparations in a competitive, concentration-dependent manner at a single class of binding sites (Ki approximately 0.27 micxroM). Calcium channel activity was determined pharmacologically in a tissue bath with electrically stimulated rabbit right ventricular strips, KCl-induced aortic ring contraction, and 45Ca2+ uptake in K(+)-depolarized cultured rat cardiomyocytes. Amiodarone completely inhibited myocardial contraction (EC50 = 1.7 microM), completely antagonized depolarization-induced aortic ring contraction (EC50 = 24 nM), and significantly reduced (29% vs. control) 45Ca2+ uptake into cultured cells. The calcium channel blocking effects of amiodarone may contribute significantly to its pharmacologic profile.
Lubic
S P
SP
Department of Veterans Affairs Medical Center, Stanford University School of Medicine, Palo Alto, California 94304.
Nguyen
K P
KP
Dave
B
B
Giacomini
J C
JC
D000638:Amiodarone / Q000378:metabolism / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009124:Muscle Proteins / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D009568:Nitrendipine / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D014665:Vasodilator Agents; D009568:Nitrendipine; D000638:Amiodarone; D002118:Calcium