Gaba-ergic properties of baclofen in vivo and in vitro

Abstract

The effects of racemic baclofen (β-p-chlorphenyl GABA) and muscimol in a GABA-dependant rotational behaviour model were compared. After unilateral intranigral injection, both compounds induced contralateral turning, but comparison of log dose-response curves indicated baclofen to be a weak partial agonist of the nigral GABA receptor, d- and l-baclofen were equiactive, as was its m-chloro-substituted analogue, β-phenylethylamine was inactive. d-and l-baclofen were equiactive (IC50, 38μM) in displacing low affinity 3H-GABA binding to a crude membrane preparation, but were inactive in displacing high affinity 3H-GABA binding to triton-treated membranes. The seemingly weak, non-stereospecific GABAergic activity of baclofen at a population of low affinity 3H-GABA binding sites is in contrast to the potent stereospecific neuronal depressant effects of l-baclofen that are not mediated by a GABAergic mechanism. This duplicity of action may account in part for the debate on the pharmacology of baclofen.