title: Long-lasting inhibition of in vivo cocaine binding to dopamine transporters by 3 beta-(4-iodophenyl)tropane-2-carboxylic acid methyl ester: RTI-55 or beta CIT.
abstract: Cocaine analogs such as 3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (RTI-55 or beta CIT) with a higher affinity for the dopamine transporter (DAT) may be potentially useful in interfering with cocaine's actions in brain. This study evaluates the time course of the effects of RTI-55 on cocaine binding in baboon brain using PET and [11C]cocaine. [11C]Cocaine binding was measured prior to, and 90 minutes, 24 hours, 4-5 days and 11-13 days after RTI-55 (0.3 mg/kg i.v.). Parallel studies with [3H]cocaine and RTI-55 (0.5 mg/kg i.v. or 2 mg/kg i.p.) were performed in the mouse. RTI-55 significantly inhibited [11C]cocaine binding at 90 minutes and 24 hours after administration. The half-life for the clearance of RTI-55 from the DAT was estimated to be 2 to 3 days in the baboon brain. In the mouse brain, RTI-55 significantly inhibited [3H]cocaine binding at 60 and 180 minutes after administration and recovery was observed at 12 hours. These results document long-lasting inhibition of cocaine binding by RTI-55 and corroborate that binding kinetics of RTI-55 in striatum observed in imaging studies with [123I]RTI-55 represents binding to DATs.
authors.affiliation: Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
authors.forename: N D
authors.initials: ND
authors.lastname: Volkow
authors.forename: S J
authors.initials: SJ
authors.lastname: Gatley
authors.forename: J S
authors.initials: JS
authors.lastname: Fowler
authors.forename: R
authors.initials: R
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Logan
authors.forename: S L
authors.initials: SL
authors.lastname: Dewey
authors.forename: Y S
authors.initials: YS
authors.lastname: Ding
authors.forename: N
authors.initials: N
authors.lastname: Pappas
authors.forename: P
authors.initials: P
authors.lastname: King
authors.forename: R R
authors.initials: RR
authors.lastname: MacGregor
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins; D010215:Papio; D013997:Time Factors; D014055:Tomography, Emission-Computed
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493215:Slc6a3 protein, mouse; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine; D004298:Dopamine