Nature of the inhibition by amiodarone of isoproterenol-induced tachycardia in the dog.

Inhibition of in vivo isoproterenol-induced tachycardia by i.v. amiodarone was studied in anesthetized dogs. Significant dose-response curves to isoproterenol could not be obtained in single animals because of the time-dependent lowering of the inhibitory effect of the drug. Single isoproterenol injections after amiodarone in 105 dogs allowed dose-response curves to be obtained. The slope of these curves decreased with increasing doses of amiodarone, and the maximal rate stimulation diminished also in a dose-dependent manner. These features are consistent with a non-competitive inhibition pattern. A mechanism of the beta-adrenergic antagonism developed by amiodarone is suggested.