[(125)I]3beta-(4-ethyl-3-iodophenyl)nortropane-2beta-carboxylic acid methyl ester ([(125)I]EINT): a potent and selective radioligand for the brain serotonin transporter.
The binding characteristics of [(125)I]3beta-(4-ethyl-3-iodophenyl)nortropane-2beta-carboxylic acid methyl ester ([(125)I]EINT), a high-affinity selective ligand for the serotonin transporter (5-HTT), and its binding characteristics to rat brain membranes were determined. [(125)I]EINT binding to rat cerebral cortex membranes was saturable and reversible, and its specific binding represented approximately 90% of the total binding. [(125)I]EINT labeled a single site with K(d) = 0.22 +/- 0.03 nM and B(max) = 583 +/- 38 fmol/mg protein. Kinetic analysis revealed a t(1/2) for association and dissociation of 20 and 24 min, respectively. Pharmacological characterization of [(125)I]EINT confirmed its high specificity for the 5-HTT. The pattern of brain region distribution in vivo of intravenously administered [(125)I]EINT indicated greater accumulation of the radioligand in 5-HTT-rich brain regions. However, the signal-to-background ratio was low. Thus, [(125)I]EINT appears to be a useful radioligand for studying the 5-HTT in vitro, but it may not be a good in vivo ligand.
Navarro
H A
HA
Center for Organic and Medicinal Chemistry, Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA. han@rti.org
Xu
H
H
Zhong
D
D
Blough
B E
BE
Ross
W P
WP
Kuhar
M J
MJ
Carroll
F I
FI
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011869:Radioligand Assay; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics*
D002352:Carrier Proteins; D003042:Cocaine; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C109597:3-(4-ethyl-3-iodophenyl)nortropane-2-carboxylic acid methyl ester; C493232:Slc6a4 protein, rat