[3H]MFZ 2-12: A Novel Radioligand for the Dopamine Transporter

In an effort to develop a tritiated dopamine transporter radioligand with higher affinity than the widely used [3H]WIN 35,428, we have synthesized [3H]2β-carbomethoxy-3β-(3′,4′-dichlorophenyl)tropane ([3H]MFZ 2-12). Unlabeled MFZ 2-12 and the N-demethylated intermediate (MFZ 2-13) inhibited dopamine uptake by the human dopamine transporter with IC50ʹs of 1.1 and 1.4 nM, respectively. The N-nor-intermediate (MFZ 2-13) was treated with CT3I resulting in [3H]MFZ 2-12; S.A.=80 Ci/mmol). [3H]MFZ 2-12 reversibly bound with a KD of 2.8 nM to human dopamine transporter expressed heterologously in EM4 cells.