Linked Life Data

10634129

Source:http://linkedlifedata.com/resource/pubmed/id/10634129

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-1-28
pubmed:abstractText
Galanthamine proved effective in symptomatic treatment of senile dementia of Alzheimer's type. The aim of this study was to elucidate the metabolism of galanthamine. Two novel metabolites of galanthamine have been isolated from the urine of eight young men after single doses of 10-15 mg. Some 19.8% of the doses were excreted as O-demethylgalanthamine glucuronide, 5% as N-demethylgalanthamine, 25.1% as galanthamine, and 0.8% as epigalanthamine. After coadministration of quinidine hydrogen sulfate, which inhibits cytochrome P450 2D6 (CYP2D6) selectively, O-demethylgalanthamine glucuronide was highly diminished in urine. In vitro, human liver microsomes metabolized galanthamine to O-demethylgalanthamine with Vmax 5.2 nmol/mg protein/h and Km 187 microM. Ki of quinidine to inhibit O-demethylation was 28 nM. To inhibit cholinesterases, O-demethylgalanthamine was 10-fold more selective for acetylcholinesterase (AChE) versus butyrylcholinesterase (BuChE) than galanthamine. After glucuronidation, O-demethylgalanthamine failed to inhibit AChE and BuChE. N-Demethylgalanthamine inhibited cholinesterases less potently than galanthamine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0960-314X
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
661-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
The O-demethylation of the antidementia drug galanthamine is catalysed by cytochrome P450 2D6.
pubmed:affiliation
Department of Psychiatry, University Clinic Charité, Humboldt University, Berlin, Germany.
pubmed:publicationType
Journal Article, Clinical Trial, In Vitro