High affinity ligands for 'diazepam-insensitive' benzodiazepine receptors.

摘要: Abstract Structurally diverse compounds have been shown to possess high affinities for benzodiazepine receptors in their ‘diazepam-sensitive’ (DS) conformations. In contrast, only the imidazobenzodiazepinone Ro 15-4513 has exhibit a affinity ‘diazepam-insensitive’ (DI) conformation of receptors. We examined series 1,4-diazepines containing one or more annelated ring systems at DI and DS receptors, several 1,4-diazepinone carboxylates including 19-4603, 16-6028 15-3505 were found (K i ∼ 2.6–20 nM) DI. Nonetheless, among ligands examined, was substance with DI/DS potency ratio I: other substances had ratios ranging from 13 > 1000. Ligands moderate Di previously classified as partial agonists, antagonists, inverse agonists but behaved ‘GABA neutral’ (antagonist) The identification additional may be helpful elucidating pharmacological physiological importance these sites.