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Stereoselective R-(+) Enantiomer of HA-966 Displays Anxiolytic Effects in Rodents

Stereoselective R-(+) Enantiomer of HA-966 Displays Anxiolytic Effects in Rodents

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

Eur J Pharmacol. 1992 Apr 22;214(2-3):207-14.

PMID: 1355434

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP123931044	R(+)-HA-966		123931-04-4	Price

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