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

Jpn J Pharmacol. 1989 Mar;49(3):337-49. doi: 10.1254/jjp.49.337.

Abstract

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 [3H]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.

Publication types

  • Comparative Study

MeSH terms

  • Aggression / drug effects
  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Anticonvulsants
  • Behavior, Animal / drug effects*
  • Body Temperature / drug effects
  • Brain Chemistry / drug effects
  • Central Nervous System Depressants
  • Conflict, Psychological
  • Diazepam / pharmacology
  • Dogs
  • Hypnotics and Sedatives
  • Isoindoles
  • Macaca fascicularis
  • Male
  • Mice
  • Mice, Inbred ICR
  • Motor Activity / drug effects
  • Muscle Relaxants, Central
  • Naphthyridines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Spiro Compounds / pharmacology*

Substances

  • Anti-Anxiety Agents
  • Anticonvulsants
  • Central Nervous System Depressants
  • Hypnotics and Sedatives
  • Isoindoles
  • Muscle Relaxants, Central
  • Naphthyridines
  • Spiro Compounds
  • pazinaclone
  • Diazepam