Chlordiazepoxide displaces thyrotropin-releasing hormone (TRH) binding.

Numerous compounds were tested for their ability to displace [3H]( 3MeHis2 )TRH binding. It was found that some, but not all, benzodiazepines displaced [3H]( 3MeHis2 )TRH from its binding site. The most potent benzodiazepine was chlordiazepoxide, which had an IC50 value of 5 microM in brain tissue and an IC50 of 290 nM in pituitary tissue. Analysis of the effect produced by chlordiazepoxide showed it to be apparently noncompetitive in brain tissue but competitive in pituitary tissue. In brain tissue the Hill coefficient was less than one, whereas in pituitary tissue the Hill coefficient was approximately 1.0. In both tissues the effect was reversible and unaffected by the presence of 10(-4) M GABA or 10(-4) M flunitrazepam. These data indicate that there exists some differences between the brain and pituitary TRH receptor complex, that the inhibition produced by chlordiazepoxide is not mediated via a classical benzodiazepine receptor and the effect of chlordiazepoxide may be of pharmacological relevance.