Heterocyclic GABA analogues as new selective inhibitors of astroglial GABA transport

A series of heterocyclic GABA analogues were tested as inhibitors of neuronal and glial GABA transport and GABA‐receptor binding. Four compounds were shown to be selective inhibitors of glial GABA uptake, and the inhibition was in each case of the competitive type. The compounds are: β‐proline, homonipecotic acid, and the bicyclic isoxazoles THPO and THAO, the K j values for the glial uptake of these compounds were 400, 700, 550, and 600 μM, respectively. The two latter compounds may be putative anticonvulsant drugs since they are likely to cross the blood‐brain barrier, and since they almost exclusively interfere with glial GABA uptake, which presumably would lead to increased synaptic GABA levels in vivo.