Interaction of AOA 39, D600, verapamil and diltiazem with cardiac cholinergic effects.

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.