title: Displacement of RTI-55 from the dopamine transporter by cocaine.
abstract: 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.
authors.affiliation: Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. gatley@brain.med.bnl.gov
authors.forename: S J
authors.initials: SJ
authors.lastname: Gatley
authors.forename: N D
authors.initials: ND
authors.lastname: Volkow
authors.forename: R
authors.initials: R
authors.lastname: Chen
authors.forename: J S
authors.initials: JS
authors.lastname: Fowler
authors.forename: F I
authors.initials: FI
authors.lastname: Carroll
authors.forename: M J
authors.initials: MJ
authors.lastname: Kuhar
mesh_terms: 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
chemical_list: 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