Enhancement of GABAergic inhibition: a mechanism of action of benzodiazepines, phenobarbital, valproate and L-cycloserine in the cat spinal cord.

Unanaesthetized spinal cats were used to assess the effects of several central depressant drugs on GABA-mediated presynaptic inhibition. Benzodiazepines enhance GABAergic inhibition by interaction with specific receptors in the spinal cord. Phenobarbital facilitates GABAergic inhibition by a mechanism unrelated to that of benzodiazepines, perhaps by an effect on the Cl- ionophore within the GABA-benzodiazepine-barbiturate receptor complex. A similar mechanism or the inhibition of GABA re-uptake might be responsible for the facilitating effect of valproate on GABA transmission. By selectively inhibiting GABA transaminase, L-cycloserine presumably increases the amount of GABA available for release.