Inhibition by neuroleptics of uptake of 3H-GABA into rat brain synaptosomes.

Neuroleptics from various chemical groups and some amino acids were examined for GABA uptake-inhibiting properties in rat brain synaptosomes. The phenothiazine and thioxanthene neuroleptics inhibited GABA uptake by 50% in the concentration range of 10-30 micron. No difference in potency was found between the cis and the trans isomers of the thioxanthenes. Clozapine and particularly sulpiride were weak inhibitors of the GABA uptake process, whereas some of the butyrophenones examined exhibited rather potent effect. Secific GABA uptake inhibitors (nipecotic acid and guvacine) were as active as the most potent butyrophenones. As no significant correlation was obtained between GABA uptake-inhibiting effect of the neuroleptics and their clinical or pharmacological effects it is concluded that the influence on GABA uptake is not an important aspect of the neuroleptic action.