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

1 The hypothesis that the antiarrhythmic drug amiodarone slows down the heart rate by its inhibitory action on the intracellular conversion of thyroxine (T 4 ) to 3,5,3′ triiodothyronine (T 3 ) was investigated. For this purpose we compared the effect of amiodarone with that of another potent inhibitor of the T 4 → T 3 conversion, i.e. the radiographic contrast medium iopanoic acid, on the heart rate of unanaesthetized guinea‐pigs. 2 Both amiodarone and, to an even greater extent, iopanoic acid induced an increase in serum 3.5′,3′ triiodothyronine (reverse T 3 ), indicating effective inhibition of T 4 → T 3 conversion. Both amiodarone and iopanoic acid were accumulated in the liver and in the heart (measured as iodine). 3 While amiodarone induced bradycardia, iopanoic acid did not change the heart rate. 4 Supraphysiological amounts of exogenous T 3 reverted the amiodarone induced bradycardia to near normal values. A comparable effect was observed with isoprenaline. 5 The intracellular inhibition of the T 4 → T 3 conversion is not the ultimate mode of the action of the amiodarone effect on heart rate. It is thought that amiodarone interacts with T 3 at its receptor or somewhere later along the pathway from the T 3 ‐receptor interaction to the final effect of T 3 on heart rate.