[H-3]MFZ 2-12: A novel radioligand for the dopamine transporter

In an effort to develop a tritiated dopamine transporter radioligand with h igher affinity than the widely used [H-3]WIN 35,428, we have synthesized [H -3]3 beta -carbomethoxy-3 beta-(3 ' .4 ' -dichloroph ([H-3]MFZ 2 12). Unlab eled MFZ 2-12 and the N-demethylated intermediate (MFZ 2-13) inhibited dopa mine uptake by the human dopamine transporter with IC50's of 1.1 and 1.4 nM , respectively. The N-nor-intermediate (MFZ 2-13) was treated with CT,I res ulting in [H-3]MFZ 2-12, S.A. = 80 Ci/mmol). [H-3]MFZ 2-12 reversibly bound with a KD of 2.8 nM to human dopamine transporter expressed heterologously in EM4 cells. Published by Elsevier Science Ltd.