title: A major metabolite of bupropion reverses motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets.
abstract: The atypical antidepressant, bupropion, causes a partial reversal of motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates. However, its monoamine uptake blocking actions are believed to be mediated by the major metabolites, racemic (-)-(2R,3R)-2-(3-chlorophenyl-3,5,5-trimethyl-2-morphinol) (R,R-hydroxybupropion) and (+)-(2S,3S)-2-(3-chlorophenyl-3,5,5-trimethyl-2-morphinol) (S,S-hydroxybupropion). Therefore, we have evaluated the ability of enantiomers to improve locomotor activity and motor disability in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets. Bupropion produced a little increase in locomotor activity and a more pronounced improvement in motor disability. The S,S-hydroxybupropion, but not the R,R-hydroxybupropion, enantiomer dose-dependently increased both locomotor activity and reversed motor disability. Combined administration of S,S-hydroxybupropion and R,R-hydroxybupropion at the same dose (analogous to the racemate) again improved motor function and to the same extent as produced by S,S-hydroxybupropion alone. The data suggest that the S,S-enantiomer of hydroxybupropion may possess potential antiparkinsonian activity.
authors.affiliation: Neurodegenerative Diseases Research Group, School of Biomedical and Health Sciences, King's College, London, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hansard
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Jackson
authors.forename: Lance A
authors.initials: LA
authors.lastname: Smith
authors.forename: Sarah
authors.initials: S
authors.lastname: Rose
authors.forename: Peter
authors.initials: P
authors.lastname: Jenner
mesh_terms: D000818:Animals; D016642:Bupropion / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D002144:Callithrix; D004305:Dose-Response Relationship, Drug; D005260:Female; D007980:Levodopa / Q000494:pharmacology; D020267:MPTP Poisoning / Q000188:drug therapy*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D013237:Stereoisomerism
chemical_list: D016642:Bupropion; D007980:Levodopa; C496215:radafaxine