Thyroid Hormones and Derivatives Inhibit Flunitrazepam Binding

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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.