title: Synthesis and monoamine transporter affinity of 2beta-carbomethoxy-3beta-(4'-p-substituted phenyl)-piperidine analogs of cocaine.
abstract: A series of novel piperidine based analogs of cocaine was synthesized and evaluated in vitro against the three monoamine transporters to develop new potential selective SERT radiotracers. Modification of the phenyl substitution with five-membered heterocyclic groups resulted in a wide affinity and selectivity scale. Radiolabeling and mouse in vivo study was performed on the piperidine analog of ZIENT, which crossed the blood-brain barrier but failed to selectively accumulate in the regions of the brain rich in SERT.
authors.affiliation: Yale University, School of Medicine, VA Connecticut HCS, 116A2, 950 Campbell Avenue, 06516, USA.
authors.forename: Frederic
authors.initials: F
authors.lastname: Bois
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: Nora S
authors.initials: NS
authors.lastname: Kula
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Baldessarini
authors.forename: M
authors.initials: M
authors.lastname: Al Tikriti
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
authors.forename: Gilles D
authors.initials: GD
authors.lastname: Tamagnan
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D051379:Mice; D050479:Neurotransmitter Transport Proteins / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011849:Radioactive Tracers; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014326:Tropanes
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D050479:Neurotransmitter Transport Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010880:Piperidines; D011849:Radioactive Tracers; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D014326:Tropanes; D003042:Cocaine