[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.
Newman
A H
AH
Medicinal Chemistry Section, National Institute on Drug Abuse-Intramural Research Program, 5500Nathan Shock Drive, MD 21224, Baltimore, USA. anewman@intra.nida.gov
Zou
M F
MF
Ferrer
J V
JV
Javitch
J A
JA
D002352:Carrier Proteins / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011869:Radioligand Assay; D014316:Tritium; D014326:Tropanes / Q000378:metabolism*
C434646:2-carbomethoxy-3-(3',4'-dichlorophenyl)tropane; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D014326:Tropanes; D014316:Tritium