Linked Life Data

15132713

Source:http://linkedlifedata.com/resource/pubmed/id/15132713

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-5-10
pubmed:abstractText
The deficiency in cholinergic neurotransmission in Alzheimer's disease has led to the development of cholinesterase inhibitors as the first-line treatment for symptoms of this disease. The clinical benefits of these agents include improvements, stabilisation or less than expected decline in cognition, function and behaviour. The common mechanism of action underlying this class of agents is an increase in available acetylcholine through inhibition of the catabolic enzyme, acetylcholinesterase. There is substantial evidence that the cholinesterase inhibitors, including donepezil, galantamine and rivastigmine, decrease acetylcholinesterase activity in a number of brain regions in patients with Alzheimer's disease. There is also a significant correlation between acetylcholinesterase inhibition and observed cognitive improvement. However, the cholinesterase inhibitors are reported to have additional pharmacological actions. Rivastigmine inhibits butyrylcholinesterase with a similar affinity to acetylcholinesterase, although it is not clear whether the inhibition of butyrylcholinesterase contributes to the therapeutic effect of rivastigmine. Based on data from preclinical studies, it has been proposed that galantamine also potentiates the action of acetylcholine on nicotinic receptors via allosteric modulation; however, the effects appear to be highly dependent on the concentrations of agonist and galantamine. It is not yet clear whether these concentrations are related to those achieved in the brain of patients with Alzheimer's disease within therapeutic dose ranges. Preclinical studies have shown that donepezil and galantamine also significantly increase nicotinic receptor density, and increased receptor density may be associated with enhanced synaptic strengthening through long-term potentiation, which is related to cognitive function. Despite these differences in pharmacology, a review of clinical data, including head-to-head studies, has not demonstrated differences in efficacy, although they may have an impact on tolerability. It seems clear that whatever the subsidiary modes of action, clinical evidence supporting acetylcholinesterase inhibition as the mechanism by which cholinesterase inhibitors treat the symptoms of Alzheimer's disease is accumulating. Certainly, as a class, the currently approved cholinesterase inhibitors (donepezil, galantamine, rivastigmine and tacrine) provide important benefits in patients with Alzheimer's disease and these drugs offer a significant advance in the management of dementia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1170-229X
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Adis Data Information BV
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
453-78
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Cholinesterase inhibitors used in the treatment of Alzheimer's disease: the relationship between pharmacological effects and clinical efficacy.
pubmed:affiliation
Memory Assessment and Research Centre, Moorgreen Hospital, Southampton, UK. david.wilkinson@wht.nhs.uk
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't