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 (K_D) of the [³H]flunitrazepam binding increased and the receptor density (B_max) decreased as a function of D-thyroxine concentration; this is characteristic of mixed-type inhibition.