In vivo labeling of the central GABA uptake carrier with super(3)H-tiagabine

The in vivo binding of super(3)H-Tiagabine to the central GABA uptake carrier in mouse brain was characterized. super(3)H-Tiagabine in vivo bound to a single class of binding sites with a K sub(d) = 72.5 nM and a B sub(max) = 640 pmol/g tissue. super(3)H-Tiagabine binding in vivo was regionally distributed within the CNS, and showed a good correlation with super(3)H-Tiagabine binding in vitro. Pharmacological characterization of super(3)H-Tiagabine binding in vivo revealed a binding site exhibiting specificity for GABA uptake inhibitors. Experiments examining the in vivo receptor occupancy of the GABA uptake carrier for a series of GABA uptake inhibitors revealed that 20-30% of the GABA uptake sites were occupied at the ED sub(50) for inhibiting DMCM-induced clonic convulsions, while a 50-62% receptor occupancy in vivo was needed to inhibit rotarod performance.