Archives internationales de pharmacodynamie et de thérapie vol:286 issue:1 pages:71-84
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.