Does Amiodarone Inhibit T₃ Binding to Solubilized Nuclear Receptors In Vitro?

Summary

One of the proposed mechanisms of action of amiodarone is by interfering with T₃-receptor interactions. However, reports in the literature on this matter are contradictory and, in an attempt to resolve these contradictions, the effects of amiodarone on T₃ binding to solubilized nuclear receptors from rat liver were investigated. A drug concentration-related competitive inhibition of T₃ binding occurred in the presence of considerable amiodarone precipitation. Measurement of the proportion of soluble amiodarone over the range where significant inhibition of T₃ binding was observed, revealed that the soluble amiodarone decreased over this range. Since the amiodarone preparation was free of any contaminant, these findings suggested that a product generated from amiodarone during incubation was responsible for the inhibition. HPLC analysis of the soluble amiodarone fraction indicated that, during incubation, two substances were generated from the parent compound. However, only the concentration of one of the substances continually increased whereas the other decreased with increasing concentrations of amiodarone added to the samples. These findings suggest that the inhibition of T₃ binding to solubilized nuclear receptors in the presence of amiodarone results from the generation of a specific product from the amiodarone under certain conditions during incubation.

Key-Words

Amiodarone - T₃ Nuclear Receptors - Amiodarone Stability - T₃ Antagonist