VTechWorks staff will be away for the winter holidays starting Tuesday, December 24, 2024, through Wednesday, January 1, 2025, and will not be replying to requests during this time. Thank you for your patience, and happy holidays!
 

Synthetic and metabolic studies on 1-methyl-4-(1-methylpyrrol-2-yl)-1,2,3,6-tetrahydropyridine, a neurotoxic analog of the Parkinsonian inducing agent MPTP

Simple item page
dc.contributor.authorBai, Hongen
dc.contributor.committeechairCastagnoli, Neal Jr.en
dc.contributor.committeememberMerola, Joseph S.en
dc.contributor.committeememberBecker, David A.en
dc.contributor.departmentChemistryen
dc.date.accessioned2014-03-14T21:42:08Zen
dc.date.adate2009-08-04en
dc.date.available2014-03-14T21:42:08Zen
dc.date.issued1991-12-02en
dc.date.rdate2009-08-04en
dc.date.sdate2009-08-04en
dc.description.abstract1-Methyl-4-(1-methylpyrrol-2-yl)-1 ,2,3,6-tetrahydropyridine (TMMP) is a neurotoxic analog of the parkinsonian inducing agent MPTP. TMMP and its putative metabolites 1-methyl-4-(1-methylpyrrol-2-yl)-2,3-dihydropyridinium (MMDP+) and 1-methyl-4-(1-methylpyrrol-2-yl)pyridinium (MMP+) were synthesized and fully characterized. Substrate/inactivation properties of TMMP and its analog N-propargyl-4-(1-methylpyrrol-2-yl)-1,2,3,6-tetrahydropyridine with MAO-B were investigated. Kinetic data was obtained, including Km and Vmax for TMMP as an MAO-B substrate, and KI and kinact values for N-propargyl-4-(1-methylpyrrol-2-yl)-1,2,3,6-tetrahydropyridine. The metabolic studies of TMMP and MMDP+ were conducted with an HPLC diode array assay. Both in-vivo and in-vitro metabolic studies showed that TMMP is oxidized to its dihydropyridinium species (MMDP+) in a reaction catalyzed by MAO-B. MMDP+ undergoes autoxidation to form the pyridinium species (MMP+), the mechanism of this conversion is not clear. In-vitro studies show that MAO-B is not responsible for this conversion and the oxidation of MMDP+ to MMP+ is likely to be enzyme catalyzed. Toxicity investigations include dopamine depletion studies of TMMP and MMDP+, mitochondrial respiration and microdialysis studies of MMDP+ and MMP+. The above studies show that TMMP is an MPTP-type neurotoxin.en
dc.description.degreeMaster of Scienceen
dc.format.extent123 leavesen
dc.format.mediumBTDen
dc.format.mimetypeapplication/pdfen
dc.identifier.otheretd-08042009-040225en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-08042009-040225/en
dc.identifier.urihttp://hdl.handle.net/10919/44138en
dc.language.isoenen
dc.publisherVirginia Techen
dc.relation.haspartLD5655.V855_1991.B34.pdfen
dc.relation.isformatofOCLC# 25490710en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subject.lccLD5655.V855 1991.B34en
dc.subject.lcshMethylphenyltetrahydropyridineen
dc.subject.lcshParkinson's diseaseen
dc.titleSynthetic and metabolic studies on 1-methyl-4-(1-methylpyrrol-2-yl)-1,2,3,6-tetrahydropyridine, a neurotoxic analog of the Parkinsonian inducing agent MPTPen
dc.typeThesisen
dc.type.dcmitypeTexten
thesis.degree.disciplineChemistryen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
LD5655.V855_1991.B34.pdf
Size:
4.14 MB
Format:
Adobe Portable Document Format
Description:
Download

Collections

Masters Theses