Pregabalin may represent a novel class of anxiolytic agents with a broad spectrum of activity.
The present study examines the effect of pregabalin (previously S-Isobutylgaba and CI-1008) in two distinct rat models of anxiety. Pregabalin binds with high affinity and selectivity to the alpha(2)delta subunit of voltage dependent calcium channels (VDCC). Its corresponding R-enantiomer (R-isobutylgaba) is approximately 10 fold weaker. Pregabalin dose-dependently induced anxiolytic-like effects in both the rat conflict test and elevated X-maze with respective minimum effective doses (MED) of 3 and 10 mg kg(-1). In contrast, R-isobutylgaba only showed activity at the highest dose of 100 mg kg(-1) in the conflict test. These data indicate that pregabalin may possess clinical utility as a novel anxiolytic agent and demonstrates the importance of the alpha(2)delta subunit of VDCC in the mediation of anxiety related behaviours.
Field
M J
MJ
Department of Biology, Pfizer Global Research and Development, Cambridge Laboratories, Forvie Site, Robinson Way, Cambridge, CB2 2QB.
Oles
R J
RJ
Singh
L
L
D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D002707:Chlordiazepoxide / Q000494:pharmacology; D003220:Conflict, Psychological; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D000069583:Pregabalin; D051381:Rats; D013237:Stereoisomerism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D015220:Calcium Channels; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D002707:Chlordiazepoxide