Pharmacology of (+)- and (-)-baclofen: GABA-dependant rotational behaviour and [3H]GABA receptor binding studies.

(+)- and (-)-baclofen were equiactive in inducing contralateral rotational behaviour following their unilateral injection into the zona reticulata of the rat substantia nigra, a proposed GABA-dependent rotational behaviour model, and in displacing the specific binding of [3H]GABA to frozen and thawed membrane preparations of rat brain. These non-stereospecific actions of baclofen at a population of cerebral GABA receptors contrast with stereospecific neuronal depressant effects probably mediated via presynaptic inhibition of the release of excitatory amino acid neurotransmitters. The present results indicate that baclofen may have two distinct mechanisms of action and this may account for the debate on the pharmacology of this compound.