Synthesis of 3H-labeled N-(3-iodoprop-2E-enyl)-2beta-carbomethoxy-3beta-(4-methylphenyl)nortropane (PE2I) and its interaction with mice striatal membrane fragments.
PE2I is a high-affinity dopamine transporter (DA(T)) ligand that exhibits high selectivity for the DA(T) over the serotonin (5-HT(T)) and norephinephrine transporter (NE(T)) making its carbon-11 and iodine-125 labeled forms very useful for quantification of DA(T) binding sites in vivo. In this paper, we reported the synthesis of tritium-labeled PE2I, as well as improvements in the preparation of its acid precursor and PE2I itself with significant improvement in the total yield compared to previously published results. The new radioligand was evaluated as a tool for assessing DA(T) binding sites in vitro. The radioligand binding to mice striatal membranes demonstrated a homogeneous population of DA(T) binding sites with the K(d) value 9 nM.
Stepanov
Vladimir
V
Institute of Organic and Bioorganic Chemistry, University of Tartu, 2 Jakobi Str, 51014 Tartu, Estonia. vladimir.stepanov@ut.ee <vladimir.stepanov@ut.ee>
Schou
Magnus
M
Järv
Jaak
J
Halldin
Christer
C
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D007553:Isotope Labeling / Q000379:methods*; D051379:Mice; D009662:Nortropanes / Q000138:chemical synthesis* / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000378:metabolism; D014316:Tritium
D050483:Dopamine Plasma Membrane Transport Proteins; C113010:N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane; D009662:Nortropanes; D019275:Radiopharmaceuticals; D014316:Tritium