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

Abstract

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.

• Authors: R 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
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 214 Issue 2-3 Pg. 207-14 (Apr 22 1992) ISSN: 0014-2999 [Print] Netherlands
• PMID: 1355434 (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

Topics

• 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