GABAB receptor antagonism by resolved (R)-saclofen in the guinea-pig ileum.
The GABAB receptor antagonist saclofen (3-amino-2-(4-chlorophenyl)propylsulphonic acid) has been resolved by chiral high-performance liquid chromatography. The enantiomer (R)-saclofen, but not (S)-saclofen, reversibly antagonised the (R,S)-baclofen-induced depression of cholinergic twitch contractions in the guinea-pig ileum with an apparent pA2 of 5.3. Also, 2-hydroxy-saclofen was resolved by the same method, its (S)-enantiomer yielding an apparent pA2 of 5.0. This method provides a convenient resolution of these antagonists.
Kerr
D I
DI
Department of Anaesthesia and Intensive Care, University of Adelaide, South Australia, Australia. dkerr@medicine.adelaide.edu.au
Ong
J
J
Vaccher
C
C
Berthelot
P
P
Flouquet
N
N
Vaccher
M P
MP
Debaert
M
M
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D018756:GABA Antagonists / Q000494:pharmacology*; D058788:GABA-B Receptor Antagonists; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D013237:Stereoisomerism
D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D001418:Baclofen; C080629:saclofen