[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 [(3)H]WIN 35,428, we have synthesized [(3)H]2beta-carbomethoxy-3beta-(3',4'-dichlorophenyl)tropane ([(3)H]MFZ 2-12). Unlabeled MFZ 2-12 and the N-demethylated intermediate (MFZ 2-13) inhibited dopamine uptake by the human dopamine transporter with IC(50)'s of 1.1 and 1.4nM, respectively. The N-nor-intermediate (MFZ 2-13) was treated with CT(3)I resulting in [(3)H]MFZ 2-12; S.A.=80 Ci/mmol). [(3)H]MFZ 2-12 reversibly bound with a K(D) of 2.8nM to human dopamine transporter expressed heterologously in EM4 cells.