Syntheses of fluorine-18 labeled inhibitors of GABA (γ-aminobutyric acid) reuptake

GABA (γ-aminobutyric acid) is a major inhibitory neurotransmitter. GABA is involved in the control of neuronal activity in the central nervous system, and dysfunctions of the GABA system have been implicated in a number of neurological disorders, particularly epilepsy and other seizure disorders. To study the GABA system in vivo using PET, previous investigators have prepared a variety of radiolabeled ligands known to bind to the GABA/benzodiazepine receptor complex. In order to examine the presynapotic physiology of the GABA system, and perhaps assess the degeneration of GABAergic neurons in desease, the authors have now prepared fluorine-18 radiotracers with demonstrated affinity for the presynaptic reuptake system for GABA. The compounds, diarylmethoxyalkyl derivatives of the amino acid nipecotic acid (1,2,3), are sufficiently non-polar to penetrate the blood-brain barrier, and are potent in vivo inhibitors of GABA reuptake