title: Reinforcing effect of pseudoephedrine isomers and the mechanism of action.
abstract: It has been proposed that ephedrine and its isomers may have abuse potential. When made available to rhesus monkeys (n = 4) for self-administration, +-pseudoephedrine functioned as a positive reinforcer in all monkeys, as did (-)-pseudoephedrine in two of three monkeys. Pseudoephedrine isomers were 10- to 33-fold less potent than cocaine. In in vitro binding in monkey brain tissue, both isomers had low affinity for dopamine and serotonin transporters by at least 200-fold relative to cocaine, but comparable affinity for norepinephrine transporters. +-Pseudoephedrine also blocked dopamine uptake in 293 hDAT cells with low potency relative to cocaine. When given in vivo +-pseudoephedrine significantly displaced radioligand binding to dopamine transporters with a potency comparable to that in self-administration. Therefore, pseudoephedrine isomers can function as reinforcers and the mechanism at dopamine transporters may underlie this effect. However, pseudoephedrine appears to be a weak reinforcer and may have relatively low abuse potential.
authors.affiliation: Department of Psychiatry and Pharmacology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
authors.forename: Sunmee
authors.initials: S
authors.lastname: Wee
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Ordway
authors.forename: William L
authors.initials: WL
authors.lastname: Woolverton
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002460:Cell Line; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004809:Ephedrine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007260:Infusion Pumps; D007536:Isomerism; D008253:Macaca mulatta; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration / Q000379:methods; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters / Q000187:drug effects / Q000378:metabolism; D014316:Tritium
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; C493232:Slc6a4 protein, rat; D027981:Symporters; D014316:Tritium; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D004809:Ephedrine; D003042:Cocaine; D004298:Dopamine