DIAZEPAM COMPETES FOR THYROXINE BINDING SITES

¹ State University of New York at Buffalo, Department of Medicine, Buffalo, New York

Competitive binding of diazepam to serum thyroxine binding sites was predicted from recently demonstrated steric similarities between diazepam and diphenyihydantoin, a chemically dissimilar anticonvulsant, which is a known competitor for thyroxine binding sites. Electrophoresis of serum containing isotopically labeled thyroid hormones indicated that diazepam, like diphenylhydantoin, displaces thyroxine from thyroxine-binding globulin to albumin and thyroxine-binding prealbumin. Triiodothyronine is displaced to albumin. Diazepam did not decrease the maximal binding capacity of thyroxine-binding globulin and its effect on thyroxine binding was reversed by dialysis. Ratios of free/bound thyroxine and triiodothyronine, determined in pooled sera at pH 7.4 and 37°C, were increased to a greater extent by diazepam than by equimolar concentrations of diphenylhydantoin. The effect of diphenylhydantoin on free/bound ratios was diminished in the presence of diazepam. Structural similarities between diazepam, diphenylhydantoin and the thyroid hormones are sufficient to permit binding to the same site on thyroxine-binding globulin.

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				G. C. Schussler Thyroxine-Binding Globulin: Specificity for the Hormonally Active Conformation of Triiodothyronine Science, October 13, 1972; 178(4057): 172 - 174. [Abstract] [PDF]