Advances in the treatment of Alzheimer's disease: benefits of dual cholinesterase inhibition.
Cholinesterase inhibitors have produced the best evidence of clinical efficacy for treating patients with Alzheimer's disease (AD). Many of these drugs selectively inhibit acetylcholinesterase (AChE), but agents that also target butyrylcholinesterase (BuChE) may provide added benefits. As AD progresses, ACh regulation may become increasingly dependent on BuChE and dual inhibitors may provide more sustained efficacy than AChE-selective agents. Dual inhibition may also help to slow the formation of amyloidogenic compounds, providing an important disease-modifying mechanism. Rivastigmine is a dual inhibitor that has demonstrated benefits across the spectrum of AD severity and across the cognitive, functional and behavioural domains of AD. It is a priority for future clinical trials to determine whether agents with dual inhibition properties have greater clinical efficacy.
Ballard
C G
CG
Newcastle General Hospital, Newcastle-upon-Tyne, UK. C.G.Ballard@newcastle.ac.uk
D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology*; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002219:Carbamates / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D048448:Phenylcarbamates; D000068836:Rivastigmine
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D000068836:Rivastigmine