Monoamine oxidase (MAO) is a mitochondrial enzyme that inactivates dopamine, noradrenaline, and serotonin in the brain (1, 2). Two isoforms, A and B, of the enzyme have been identified. MAO-A preferentially oxidizes serotonin and noradrenaline, whereas MAO-B preferentially oxidizes phenethylamine. Dopamine is a substrate for both enzymes. MAO-A is predominately associated with depression and anxiety disorders, whereas MAO-B is predominately associated with neurodegenerative diseases, such as Parkinson’s disease (PD), as indicated by studies with specific MAO isoform inhibitors (3-5). MAO-A is selectively inhibited by clorgyline, whereas MAO-B is selectively and irreversibly inhibited by L-depreny. In the human brain, MAO-B predominates and is present in both glial cells and neurons (6), most abundantly in serotonin and histamine neurons (7).
(S)-5-Methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)-benzo[d]isoxazol-3-yl]-oxazolidin-2-one (SL25.1188) is a selective and reversible MAO-B inhibitor (8). For measurements of MAO-B activity, (S)-5-methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)benzo[d]isoxazol-3-yl]-oxazolidin-2-[11C]one ([11C]SL25.1188) has been prepared for use in positron emission tomography (PET) studies.