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Several centrally active benzodiazepines (BZ) were tested for their ability to inhibit the TRH-induced secretion of TSH in vitro from perifused pituitaries. Diazepam, flurazepam, chlordiazepoxide (CDZ) and midazolam (10 nM) inhibited the TSH response to TRH (10 nM) by 33-50%, while medazepam, a prodrug having virtually no affinity for central BZ sites, did not. CDZ inhibition was reversed by Ro 15-1788, antagonist of the central type BZ binding sites, but not by PK 11195, antagonist of the peripheral type. The data are consistent with an involvement of central type BZ receptor sites in the TSH-lowering effects of BZ in rats.
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