| dc.contributor |
Wichita State University. Department of Chemistry |
en_US |
| dc.contributor.author |
Wimalasena, D. Shyamali |
en_US |
| dc.contributor.author |
Perera, Rohan P. |
en_US |
| dc.contributor.author |
Heyen, Bruce J. |
en_US |
| dc.contributor.author |
Balasooriya, Inoka S. |
en_US |
| dc.contributor.author |
Wimalasena, Kandatege |
en_US |
| dc.date.accessioned |
2012-02-06T17:17:31Z |
|
| dc.date.available |
2012-02-06T17:17:31Z |
|
| dc.date.issued |
2008-02-28 |
en_US |
| dc.identifier |
18220329 |
en_US |
| dc.identifier |
9716531 |
en_US |
| dc.identifier |
NS 39423 |
en_US |
| dc.identifier.citation |
Journal of medicinal chemistry. 2008 Feb 28; 51(4): 760-8. |
en_US |
| dc.identifier.issn |
0022-2623 |
en_US |
| dc.identifier.uri |
http://dx.doi.org/10.1021/jm070875p |
en_US |
| dc.identifier.uri |
http://hdl.handle.net/10057/4434 |
|
| dc.description |
Click on the DOI link below to access the article (may not be free). |
en_US |
| dc.description.abstract |
The 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.sponsorship |
NINDS NIH HHS |
en_US |
| dc.format.extent |
760-8 |
en_US |
| dc.language.iso |
eng |
en_US |
| dc.publisher |
American Chemical Society |
en_US |
| dc.relation.ispartofseries |
Journal of medicinal chemistry |
en_US |
| dc.relation.ispartofseries |
J. Med. Chem. |
en_US |
| dc.source |
NLM |
en_US |
| dc.subject |
In Vitro |
en_US |
| dc.subject |
Research Support, N.I.H., Extramural |
en_US |
| dc.subject.mesh |
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/analogs & derivatives |
en_US |
| dc.subject.mesh |
1-Methyl-4-phenylpyridinium/analogs & derivatives |
en_US |
| dc.subject.mesh |
Animals |
en_US |
| dc.subject.mesh |
Cattle |
en_US |
| dc.subject.mesh |
Chromaffin Granules/drug effects |
en_US |
| dc.subject.mesh |
Crystallography, X-Ray |
en_US |
| dc.subject.mesh |
Models, Molecular |
en_US |
| dc.subject.mesh |
Structure-Activity Relationship |
en_US |
| dc.subject.mesh |
Vesicular Monoamine Transport Proteins/antagonists & inhibitors |
en_US |
| dc.subject.mesh |
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/chemical synthesis |
en_US |
| dc.subject.mesh |
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology |
en_US |
| dc.subject.mesh |
1-Methyl-4-phenylpyridinium/chemical synthesis |
en_US |
| dc.subject.mesh |
1-Methyl-4-phenylpyridinium/pharmacology |
en_US |
| dc.subject.mesh |
Chromaffin Granules/metabolism |
en_US |
| dc.subject.mesh |
Vesicular Monoamine Transport Proteins/metabolism |
en_US |
| dc.title |
Vesicular monoamine transporter substrate/inhibitor activity of MPTP/MPP+ derivatives: a structure-activity study |
en_US |
| dc.type |
Article |
en_US |
| dc.coverage.spacial |
United States |
en_US |
| dc.description.version |
peer reviewed |
en_US |
| dc.rights.holder |
Copyright © 2008 American Chemical Society |
en_US |