Desethylamiodarone is a competitive inhibitor of the binding of thyroid hormone to the thyroid hormone alpha 1-receptor protein

Mol Cell Endocrinol. 1995 Jul;112(1):15-9. doi: 10.1016/0303-7207(95)03578-u.


Desethylamiodarone (DEA), the major metabolite of the potent antiarrythmic drug amiodarone, is a non-competitive inhibitor of the binding of thyroid hormone (T3) to the beta 1-thyroid hormone receptor (T3R). In the present study, we investigated whether DEA acts in a similar way with respect to the alpha 1-T3R. The chicken alpha 1-T3R, expressed in an E. coli system, was incubated in the presence or absence of DEA with [125I]T3 in buffer containing 0.05% Triton X-100, 0.05% BSA and 1% ethanol (v/v) in order to solubilise DEA. DEA, but not amiodarone, inhibited T3 binding in a dose-dependent manner; the IC50 value was 3.5 x 10(-5) M. Scatchard analyses in the presence of DEA demonstrated a dose-dependent decrease in Ka values, but no change in MBC. Lineweaver-Burk plots clearly indicated competitive inhibition by DEA. Pre-incubation of the alpha 1-receptor with DEA decreased maximal [125I]T3 binding, which was independent of the duration of pre-incubation. In conclusion, in contrast to the beta 1-T3R, where DEA acts as a non-competitive inhibitor, we now report as a new finding the competitive action of DEA to the alpha 1-T3R.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Amiodarone / analogs & derivatives*
  • Amiodarone / pharmacology
  • Animals
  • Binding Sites
  • Binding, Competitive
  • Chickens
  • Escherichia coli / genetics
  • Iodine Radioisotopes
  • Kinetics
  • Molecular Sequence Data
  • Receptors, Thyroid Hormone / chemistry
  • Receptors, Thyroid Hormone / genetics
  • Receptors, Thyroid Hormone / metabolism*
  • Recombinant Proteins / metabolism
  • Triiodothyronine / antagonists & inhibitors*
  • Triiodothyronine / metabolism


  • Iodine Radioisotopes
  • Receptors, Thyroid Hormone
  • Recombinant Proteins
  • Triiodothyronine
  • desethylamiodarone
  • Amiodarone