Linked Life Data

2786565

Source:http://linkedlifedata.com/resource/pubmed/id/2786565

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1989-7-21
pubmed:abstractText
In the accompanying paper, several tetrahydropyridine analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were screened for their abilities to be oxidized by monoamine oxidase (MAO) to pyridiniums and to produce neurotoxicity in mice. We reported that most of the analogs were oxidized by MAO to pyridiniums and some of the analogs were neurotoxic. We concluded that the capacity of a tetrahydropyridine MPTP analog to be oxidized by MAO to a pyridinium was a necessary, but not sufficient, condition for the compound to be a neurotoxin. In the present paper we attempt to explain further the neurotoxicity or lack of neurotoxicity of these analogs by evaluating the abilities of the pyridinium compounds to serve as substrates for the neostriatal dopamine (DA) transport system and as inhibitors of mitochondrial respiration. We now report that all of the neurotoxic MPTP analogs are oxidized to pyridiniums that are good substrates for the neostriatal DA carrier and good inhibitors of mitochondrial respiration. The results are consistent with an important role for both uptake of the pyridiniums by the DA carrier and inhibition by the pyridiniums of mitochondrial respiration in the neurotoxicity induced by MPTP and its analogs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
249
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
829-35
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Structure-activity study of the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. II. Evaluation of the biological activity of the pyridinium metabolites formed from the monoamine oxidase-catalyzed oxidation of MPTP analogs.
pubmed:affiliation
Department of Neurology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't