The (S)-enantiomer of 2-hydroxysaclofen is the active GABAB receptor antagonist in central and peripheral preparations.
In the guinea-pig isolated ileum, (RS)-(+/-)-baclofen induced a depression of cholinergic twitch contractions, reversibly and competitively antagonised by (S)-2-hydroxysaclofen (pA2 = 5.2 +/- 0.2), but not by (R)-2-hyroxysaclofen. The depression of excitatory field potentials by baclofen ( 5 mu M) in rat CA1 hippocampal slices was antagonised by (S)-2-hydroxysaclofen (100 mu m) (pA2 = 4.3), whilst in rat neocortex, (S)-2-hyroxysaclofen (50-500 mu M) antagonised the baclofen (10 mu M)-induced suppression of spontaneous discharges, the (R)-enantiomer being inactive. These results show that (S)-2-hydroxysaclofen is the active antagonist at central and peripheral GABAB receptors.
Kerr
D I
DI
Department of Anaesthesia and Intensive Care, The University of Adelaide, Adelaide, South Australia 5005, Australia.
Ong
J
J
Doolette
D J
DJ
Schafer
K
K
Prager
R H
RH
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects*; D007082:Ileum / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects*
D018080:Receptors, GABA-B; D001418:Baclofen; C057491:2-hydroxysaclofen