Home Current Issue Previous Issues Published Ahead-of-Print For Authors Journal Info
Skip Navigation LinksHome > April 2003 - Volume 17 - Issue 2 > Inhibition of Human Cholinesterases by Drugs Used to Treat A...
Alzheimer Disease & Associated Disorders:
Article

Inhibition of Human Cholinesterases by Drugs Used to Treat Alzheimer Disease

Darvesh, Sultan*†‡§; Walsh, Ryan†‡; Kumar, Rohit; Caines, Angela; Roberts, Sheila; Magee, David§; Rockwood, Kenneth*; Martin, Earl

Collapse Box

Abstract

Current approaches to the treatment of cognitive and behavioral symptoms of Alzheimer disease emphasize the use of cholinesterase inhibitors. The kinetic effects of the cholinesterase inhibitors donepezil, galantamine, metrifonate, physostigmine, rivastigmine, and tetrahydroaminoacridine were examined with respect to their action on the esterase and aryl acylamidase activities of human acetylcholinesterase (AChE) and human butyrylcholinesterase (BuChE). Each of these drugs inhibited both AChE and BuChE, but to different degrees. Inhibition of BuChE by these compounds was approximately the same, or better, when acetylthiocholine, the analog of the neurotransmitter acetylcholine, was used as the substrate, instead of butyrylthiocholine. In addition, for these drugs, the inhibition of aryl acylamidase activity paralleled that observed for inhibition of esterase activity of AChE and BuChE. Given that drugs that are currently in use for the treatment of Alzheimer disease inhibit both AChE and BuChE, the development of drugs targeted toward the exclusive inhibition of one or the other cholinesterase may be important for understanding the relative importance of inhibition of BuChE and AChE in the treatment of this disease.

© 2003 Lippincott Williams & Wilkins, Inc.

Login

Article Tools

Share

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.