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dc.contributorWichita State University. Department of Chemistryen_US
dc.contributor.authorWimalasena, D. Shyamalien_US
dc.contributor.authorPerera, Rohan P.en_US
dc.contributor.authorHeyen, Bruce J.en_US
dc.contributor.authorBalasooriya, Inoka S.en_US
dc.contributor.authorWimalasena, Kandategeen_US
dc.date.accessioned2012-02-06T17:17:31Z
dc.date.available2012-02-06T17:17:31Z
dc.date.issued2008-02-28en_US
dc.identifier18220329en_US
dc.identifier9716531en_US
dc.identifierNS 39423en_US
dc.identifier.citationJournal of medicinal chemistry. 2008 Feb 28; 51(4): 760-8.en_US
dc.identifier.issn0022-2623en_US
dc.identifier.urihttp://dx.doi.org/10.1021/jm070875pen_US
dc.identifier.urihttp://hdl.handle.net/10057/4434
dc.descriptionClick on the DOI link below to access the article (may not be free).en_US
dc.description.abstractThe active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), N-methyl-4-phenylpyridinium (MPP(+)), selectively destroys the dopaminergic neurons and induces the symptoms of Parkinson's disease. Inhibition of mitochondrial complex I and/or the perturbation of dopamine metabolism through cellular and granular accumulation have been proposed as some of the major causes of neurotoxicity. In the present study we have synthesized and characterized a number of MPTP and MPP(+) derivatives that are suitable for the comparative neurotoxicity and complex I inhibition versus dopamine metabolism perturbation studies. Structure-activity studies with bovine chromaffin granule ghosts show that 3'-hydroxy-MPP(+) is one of the best known substrates for the vesicular monoamine transporter (VMAT). A series of compounds that combine the structural features of MPP(+) and a previously characterized VMAT inhibitor, 3-amino-2-phenyl-propene, have been identified as the most effective VMAT inhibitors. These derivatives have been used to define the structural requirements of the VMAT substrate and inhibitor activities.en_US
dc.description.sponsorshipNINDS NIH HHSen_US
dc.format.extent760-8en_US
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.ispartofseriesJournal of medicinal chemistryen_US
dc.relation.ispartofseriesJ. Med. Chem.en_US
dc.sourceNLMen_US
dc.subjectIn Vitroen_US
dc.subjectResearch Support, N.I.H., Extramuralen_US
dc.subject.mesh1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/analogs & derivativesen_US
dc.subject.mesh1-Methyl-4-phenylpyridinium/analogs & derivativesen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCattleen_US
dc.subject.meshChromaffin Granules/drug effectsen_US
dc.subject.meshCrystallography, X-Rayen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshStructure-Activity Relationshipen_US
dc.subject.meshVesicular Monoamine Transport Proteins/antagonists & inhibitorsen_US
dc.subject.mesh1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/chemical synthesisen_US
dc.subject.mesh1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacologyen_US
dc.subject.mesh1-Methyl-4-phenylpyridinium/chemical synthesisen_US
dc.subject.mesh1-Methyl-4-phenylpyridinium/pharmacologyen_US
dc.subject.meshChromaffin Granules/metabolismen_US
dc.subject.meshVesicular Monoamine Transport Proteins/metabolismen_US
dc.titleVesicular monoamine transporter substrate/inhibitor activity of MPTP/MPP+ derivatives: a structure-activity studyen_US
dc.typeArticleen_US
dc.coverage.spacialUnited Statesen_US
dc.description.versionpeer revieweden_US
dc.rights.holderCopyright © 2008 American Chemical Societyen_US


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