Pharmacologic characterization of a novel non-benzodiazepine selective anxiolytic, DN-2327.

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DN-2327, 2-(7-chloro-1, 8-naphthyridin-2-yl)-3-[(1, 4-dioxa-8-azaspiro-[4, 5]dec-8-yl)carbonylmethyl]isoindolin-1-one, produced anxiolytic, taming and anti-convulsive effects when administered orally to several species of animals. DN-2327 produced few of the sedative-hypnotic and muscle-relaxant effects observed with diazepam. The durations of the anxiolytic and anti-convulsive activities of DN-2327 were much longer than those of diazepam. Tolerance to DN-2327 did not develop when it was administered daily for 14 days in an anti-conflict test (Vogel conflict test). DN-2327 showed potent displacement activity against[<SUP>3</SUP>H]diazepam binding. The binding affinity of DN-2327 for benzodiazepine receptors was about twenty times that of diazepam. Furthermore, the affinity of DN-2327 for benzodiazepine receptors was not enhanced by the presence of GABA. There is a wide margin between the doses of DN-2327 that cause the anxiolytic effects and its sedative-hypnotic/muscle-relaxant effects. These results suggest that DN-2327 has more marked anxioselective properties compared with the benzodiazepines.
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