title: Preparation and Characterization of Tetrabenazine Enantiomers against Vesicular Monoamine Transporter 2.
abstract: As a clinical medication for the treatment of hyperkinetic movement disorders, in conditions such as Huntington's disease, tetrabenazine (TBZ) has been always used in its racemic form. To establish whether or not its beneficial therapeutic actions are enantiospecific, a practical total synthetic route was developed to yield each enantiomeric form to allow their chemical and pharmacological characterization. We briefly summarize the total synthesis of TBZ and report a detailed procedure for resolution of TBZ into its enantiomers, (+)-TBZ and (-)-TBZ. This allowed determination of the optical rotation and absolute configurations of each TBZ enantiomer, based on X-ray crystallographic analysis, together with characterization of their inhibitory action at the vesicular monoamine transporter 2, where (+)-TBZ proved three-fold more active than (-)-TBZ.
authors.affiliation: Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA.
authors.forename: Qian-Sheng
authors.initials: QS
authors.lastname: Yu
authors.forename: Weiming
authors.initials: W
authors.lastname: Luo
authors.forename: Jeffery
authors.initials: J
authors.lastname: Deschamps
authors.forename: Harold W
authors.initials: HW
authors.lastname: Holloway
authors.forename: Theresa
authors.initials: T
authors.lastname: Kopajtic
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Katz
authors.forename: Arnold
authors.initials: A
authors.lastname: Brossi
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Greig