THE EFFECT OF ANTICONVULSANT DRUGS ON GABA-STIMULATED CHLORIDE UPTAKE

Eight anticonvulsant drugs - including clonazepam, diazepam and phenob arbital - were tested for their effects on GABA-stimulated chloride up take in rat cerebral cortical microsacs (unfiltered synaptoneurosomes) . ''Mid'' and ''high'' therapeutic concentrations were screened, and, if significant enhancement was found, full concentration-response test s were done. In the initial screens, enhancement of GABA-stimulated up take was found only with phenobarbital, clonazepam and diazepam. In su bsequent concentration-response tests, the effects of phenobarbital we re found to occur throughout the range of normal, anticonvulsant conce ntrations, whereas the effects of clonazepam and diazepam were observe d only above the concentrations normally used for the chronic control of seizures or anxiety. These data suggest that phenobarbital's antico nvulsant effects are mediated via the GABA, receptor complex, but that the low-dose effects of the benzodiazepines may be mediated via some other mechanism.