title: Interaction of AOA 39, D600, verapamil and diltiazem with cardiac cholinergic effects.
abstract: The influence of the organic calcium channel blockers D600 and verapamil on cardiac cholinergic effects was studied using standard electrophysiological techniques on rabbit atrial strips, and using the two-microelectrode voltage-clamp technique on rabbit Purkinje fibers. The interaction between the above drugs as well as between AQA-39, diltiazem or nifedipine and muscarinic receptors was investigated using tritiated quinuclidinylbenzilate ([3H]QNB) binding on rabbit atrial homogenates. The electrophysiological experiments show that D600 and verapamil, at high concentrations (greater than 10(-6) M), inhibit the hyperpolarization and the increase in K+ conductance induced by acetylcholine. The binding experiments show that this inhibitory action of Ca2+ antagonists is due to an interaction at the level of muscarinic receptors. All the Ca2+ channel blockers used, except nifedipine, behave like classical muscarinic antagonists as shown by a 1 to 1 reaction between drug and receptor molecules. Because of the low affinity for the interaction between the Ca2+ channel blockers and muscarinic receptors, the clinical importance of this antimuscarinic effect is probably negligible.
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004347:Drug Interactions; D005711:Gallopamil / Q000494:pharmacology; D006329:Heart Conduction System / Q000187:drug effects*; D054833:Isoindoles; D009543:Nifedipine / Q000494:pharmacology; D010797:Phthalimides / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011817:Rabbits; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D054833:Isoindoles; D010797:Phthalimides; D011976:Receptors, Muscarinic; D014316:Tritium; D005711:Gallopamil; D011813:Quinuclidinyl Benzilate; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; C030532:falipamil