1H NMR Probe for in Situ Monitoring of Dopamine Metabolism and Its Application to Inhibitor Screening

Dopamine (DA) is a monoamine neurotransmitter that plays important roles in the brain, and whose levels in the brain are associated with several neurological and psychiatric disorders. Therefore, DA metabolism inhibitors have been used as therapeutic agents. Here, we report a 1H NMR probe for the in situ analysis of DA metabolism, and its application to DA inhibitor screening. We designed doubly 13C-labeled DA (13C2-DA) as the probe. The combination of the 13C2-DA and 1H–{13C–13C′} NMR technique allowed the selective and thus in situ monitoring of DA metabolism. Using 13C2-DA, we successfully measured the efficacies of different inhibitors in a tissue sample, allowing us to improve the in situ inhibitory efficacy of the known DA metabolism inhibitor, clorgyline.