Does amiodarone affect heart rate by inhibiting the intracellular generation of triiodothyronine from thyroxine?

The hypothesis that the antiarrhythmic drug amiodarone slows down the heart rate by its inhibitory action on the intracellular conversion of thyroxine (T4) to 3,5,3' triiodothyronine (T3) was investigated. For this purpose we compared the effect of amiodarone with that of another potent inhibitor of the T4----T3 conversion, i.e. the radiographic contrast medium iopanoic acid, on the heart rate of unanaesthetized guinea-pigs. Both amiodarone and, to an even greater extent, iopanoic acid induced an increase in serum 3.5',3' triiodothyronine (reverse T3), indicating effective inhibition of T4----T3 conversion. Both amiodarone and iopanoic acid were accumulated in the liver and in the heart (measured as iodine). While amiodarone induced bradycardia, iopanoic acid did not change the heart rate. Supraphysiological amounts of exogenous T3 reverted the amiodarone induced bradycardia to near normal values. A comparable effect was observed with isoprenaline. The intracellular inhibition of the T4----T3 conversion is not the ultimate mode of the action of the amiodarone effect on heart rate. It is thought that amiodarone interacts with T3 at its receptor or somewhere later along the pathway from the T3-receptor interaction to the final effect of T3 on heart rate.