Stereoselective R-(+) enantiomer of HA-966 displays anxiolytic effects in rodents.

Anxiolytic agents disinhibit suppressed behaviors in rodents in preclinical models of anxiety such as the non-conditioned social interaction and elevated plus maze assays and the conditioned conflict Cook and Davidson procedure. The (+) and (-) enantiomers of (+/-)-3-amino-1-hydroxy-2-pyrrolidinone (HA-966) have been resolved and revealed that R-(+)-HA-966 significantly disinhibits both non-conditioned and conditioned suppressed behavior similar to the benzodiazepine diazepam, while the S-(-) enantiomer was devoid of anxiolytic activity and only produced behavioral sedation. Furthermore, R-(+)-HA-966 lacked side-effects in rodents commonly associated with the administration of benzodiazepines such as motor incoordination and ataxia, significant interactions with ethanol, and amnesia. These data suggest that R-(+)-HA-966, an antagonist at the strychnine-insensitive glycine/NMDA receptor site, was anxioselective and lacked some of the side-effects associated with benzodiazepine anxiolytics.
AuthorsR W Dunn, D M Flanagan, L L Martin, L L Kerman, A T Woods, F Camacho, C A Wilmot, M L Cornfeldt, R C Effland, P L Wood
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 214 Issue 2-3 Pg. 207-14 (Apr 22 1992) ISSN: 0014-2999 [Print] NETHERLANDS
PMID1355434 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Anti-Anxiety Agents
  • Pyrrolidinones
  • Receptors, Glycine
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • 1-hydroxy-3-amino-2-pyrrolidone
  • Diazepam
  • Animals
  • Anti-Anxiety Agents (chemistry, pharmacology)
  • Anxiety (drug therapy)
  • Behavior, Animal (drug effects, physiology)
  • Diazepam (pharmacology)
  • Male
  • Mice
  • Pyrrolidinones (chemistry, pharmacology)
  • Rats
  • Rats, Inbred Strains
  • Receptors, Glycine
  • Receptors, N-Methyl-D-Aspartate (drug effects, physiology)
  • Receptors, Neurotransmitter (drug effects, physiology)
  • Stereoisomerism

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