The (S)-enantiomer of 2-hydroxysaclofen is the active GABAB receptor antagonist in central and peripheral preparations

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1995

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Kerr, D.
Ong, J.
Doolette, D.
Schafer, K.
Prager, R.

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European Journal of Pharmacology, 1995; 287(2):185-189

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Abstract

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.

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© 1995 Elsevier Science B.V. All rights reserved

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