Linked Life Data

9784281

Source:http://linkedlifedata.com/resource/pubmed/id/9784281

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-11-25
pubmed:abstractText
The development of a validated primate model of progressive parkinsonism is a critical step in the evaluation of drugs that might halt or slow progression of Parkinson's disease. In this pilot study, we gradually exposed 14 cynomolgus monkeys to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), at a weekly dose of 0.5 mg/kg s.c. for 10 weeks, to determine their probability of not reaching a predetermined endpoint on a disability scale by Kaplan-Meier analysis. Four other MPTP-exposed animals were coadministered the potent free radical scavenger 7-hydroxy-1-[4-(3-methoxyphenyl)-1-piperazinyl]acetylamino-2,2,4,6- tetramethylindan (OPC-14117) as a single oral daily dose of 0.6 g/kg, starting 2 weeks before MPTP initiation. The risk of reaching endpoint by week 10 was 79% and mean time before reaching endpoint was 6 weeks. Global motor activity, recorded in a subset of animals using a portable activity monitor, declined following the first MPTP dose and never recovered. Several cerebrospinal fluid indices of central monoamine metabolism collected by suboccipital puncture at 0, 5, and 10 weeks, including HVA, DOPAC, and tetrahydrobiopterin but not MHPG, were found to be "trait" markers for MPTP exposure, whereas CSF DOPAC and tetrahydrobiopterin constituted potential "state" markers for reaching endpoint. The antioxidant OPC-14117 did not protect against MPTP-induced parkinsonism. Further attempts to validate this incremental model of neurotoxin-induced parkinsonism as a predictor of patient responses to putative neuroprotective agents appear warranted.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0014-4886
pubmed:author
pubmed:issnType
Print
pubmed:volume
153
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
214-22
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Chronic exposure to MPTP as a primate model of progressive parkinsonism: a pilot study with a free radical scavenger.
pubmed:affiliation
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't