Thyroid Hormones and Derivatives Inhibit Flunitrazepam Binding

Abstract: Thyroid hormones and their derivatives were found to inhibit [3H]flunitrazepam binding stereospe‐cifically and in a monophasic manner. Among the compounds tested, D‐thyroxine was the most potent inhibitor (IC50= 0.5 μM). The naturally occurring L‐thyroxine was about 40‐fold less potent (IC50= 20 μM). The structure‐activity relationships seem to imply that the thyronine base has the principal role in the inhibition of benzo‐diazepine receptor binding. The type of inhibition was examined with the most potent inhibitor, D‐thyroxine, by Scatchard analysis. The apparent dissociation constant (KD) of the [3H]flunitrazepam binding increased and the receptor density (Bmax) decreased as a function of D‐thyroxine concentration; this is characteristic of mixed‐type inhibition.