Linked Life Data

11669505

Source:http://linkedlifedata.com/resource/pubmed/id/11669505

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2001-10-23
pubmed:abstractText
Impaired cholinergic function in the central nervous system is an early feature of Alzheimer disease (AD). Currently, cholinergic deficit is usually corrected by increasing the amount of acetylcholine in the synapse by inhibiting acetylcholinesterase (AChE). One of the most consistent cholinergic deficits in AD is the reduced expression of nicotinic acetylcholine receptors (nAChR) in the brain. Since these receptors are essential for learning and memory, restoring nicotinic cholinergic function is a promising approach to treating AD. Allosteric modulation of nAChR is a novel approach, which circumvents development of tolerance through long-term use of conventional nicotinic agonists. Allosteric modulators interact with receptor-binding sites distinct from those capable of recognizing the natural agonist. Positive allosteric modulation of nAChR activity has no effect on conductance of single channels; instead, by facilitating channel opening, it potentiates responses evoked by the interaction of the natural agonist with presynaptic and postsynaptic nAChR. Allosteric modulation of nAChR activity could therefore potentially produce a significant benefit in AD. One such allosteric modulator is galantamine. In addition to increasing nAChR activity, galantamine also inhibits AChE. This novel, dual mechanism of action distinguishes galantamine from many other AChE inhibitors. Galantamine has been shown to improve cognitive and daily function for at least 6 months in placebo-controlled trials, and to maintain these functions at baseline levels for at least 12 months in a 6-month open-label extension study. Galantamine has positive effects on nAChR expression, which are likely to contribute to its sustained efficacy in the treatment of AD patients.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0893-0341
pubmed:author
pubmed:issnType
Print
pubmed:volume
15 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S19-25
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Modulation of nicotinic receptor activity in the central nervous system: a novel approach to the treatment of Alzheimer disease.
pubmed:affiliation
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201, USA. ealbuque@umaryland.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't