Displacement of RTI-55 from the dopamine transporter by cocaine.
The cocaine analog 3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (RTI-55 or beta CIT) has a higher affinity for the dopamine transporter and may be potentially useful in interfering with cocaine's actions in brain. However, imaging studies have demonstrated displacement of tracer doses of [123I]RTI-55 by a subsequent dose of cocaine. Similar displacement of pharmacological doses of RTI-55 might compromize therapy with RTI-55 in cocaine abuse. The reduction in dopamine transporter availability, assessed in vivo in mouse striatum using [3H]cocaine, caused by pretreatment with RTI-55 was significantly mitigated by subsequent administration of cocaine. In a similar experiment using a tracer dose of [123I]RTI-55 significant reductions of striatal radioligand binding by pretreatment with cocaine or RTI-55 were not observed. These results suggest that: (1) cocaine can displace pharmacological doses of RTI-55 from striatum, and (2) radioligands used to assess binding site occupancy should have a lower affinity than the occupying drug.
Gatley
S J
SJ
Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. gatley@brain.med.bnl.gov
Volkow
N D
ND
Chen
R
R
Fowler
J S
JS
Carroll
F I
FI
Kuhar
M J
MJ
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D051379:Mice; D009419:Nerve Tissue Proteins; D011869:Radioligand Assay; D014316:Tritium
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D014316:Tritium; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine; D004298:Dopamine