Abstract

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.