Benzodiazepines compete for thyrotropin-releasing hormone receptor binding: micromolar potency in rat pituitary,...

In screening neuroactive compounds for their possible interaction with rat thyrotropin-releasing hormone (TRH) receptors, some benzodiazepines were found to compete relatively potently for specific [3H](3-Me-His2)TRH [( 3H]MeTRH) binding. The profile of activity (chlordiazepoxide greater than diazepam greater than flurazepam greater than lurazepam greater than flunitrazepam) was almost identical for washed pituitary, retina and amygdala preparations. Corresponding Ki values for the latter region were (microM): 0.33, 3.24, 17.4 for the 3 most active inhibitors. Other (47) neuroactive substances exhibited little activity on [3H]MeTRH binding. All benzodiazepines tested were competitive inhibitors in the three tissues. These data support previous evidence for a close similarity of TRH receptors in the pituitary gland and central nervous system, and invoke the possibility of TRH receptor-mediated effects for some benzodiazepines.