Linked Life Data

14697898

Source:http://linkedlifedata.com/resource/pubmed/id/14697898

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2003-12-30
pubmed:abstractText
(-)-Deprenyl (selegiline) is an irreversible inhibitor of monoamine oxidase (MAO) B, which was discovered in 1962 and become the "golden standard" of MAO research. Like the other MAO-B inhibitors, it was synthesized as an antidepressant, but in a selective MAO-B inhibitory dose it does not act in depression. It is used in the treatment of Parkinson's disease. (-)-Deprenyl potentiates the effect of dopamine, it has antioxidant activity and prevents the toxicity of the dopaminergic (6-OH-dopamine; 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)), the noradrenergic (DSP-4) and cholinergic (AF64A) neurotoxins after pre-treatment. When (-)-deprenyl was administered with levodopa in a long-term treatment of Parkinsonian patients, it induces adverse events (nausea, dizziness, confusion, hallucination, insomnia and cardiovascular changes), which could be due to dopamine potentiation in dopaminergic systems (limbic system), other than the nigrostriatal pathway. (-)-Deprenyl in much lower concentrations needed to induce MAO-B inhibition (10(-9) to 10(-13) M) potently inhibits MPTP or serum withdrawal induced apoptosis in tissue cultures of neuro-ectodermal origin (PC12, M1, M2058). The (+)-enantiomer of deprenyl lacks of this property. The anti-apoptotic activity of (-)-deprenyl can be prevented by inhibiting the metabolism of the drug with SKF-525A pre-treatment, which suggests that some of the presently unknown metabolites could be responsible for the anti-apoptotic activity. In high concentration (10(-3) M), (-)-deprenyl and its metabolites induce apoptosis in tissue cultures without serum withdrawal (biphasic action). Our findings support the view that 100, or even 1000 times lower dose of (-)-deprenyl can be offered in human therapy to protect, or slow down neuronal degeneration, than it is presently used. With low dose of the drug the dopaminergic adverse events could be avoided, while anti-apoptotic activity might be preserved.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0161-813X
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
233-42
pubmed:dateRevised
2005-11-16
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
(-)-Deprenyl, a selective MAO-B inhibitor, with apoptotic and anti-apoptotic properties.
pubmed:affiliation
Department of Pharmacodynamics, Neurochemical Research Unit, Semmelweis University, Hungarian Academy of Sciences, PO Box 370, Budapest 1445, Hungary. magykal@net.sote.hu
pubmed:publicationType
Journal Article, Review