What is a Cholinesterase Inhibitor

Acetylcholine is a neurotransmitter, a chemical substance which neurons in the brain use to communicate with one another. Cholinesterase is an enzyme which normally cleans up unused acetylcholine, by breaking it down into its components acetate and choline. These components can then be recycled for later use.

Cholinesterase inhibitors are drugs that prevent (or inhibit) cholinesterase from cleaning up unused acetylcholine; the result is that individual acetylcholine molecules survive longer.

Neurons which produce acetylcholine are among the first to be damaged in Alzheimer's disease, with the result that levels of acetylcholine fall in the brain. Cholinesterase inhibitors may be useful in these patients by allowing what acetylcholine there is to survive longer and be more effective.

Cholinesterase inhibitor drugs

Four cholinesterase inhibitors:

Tacrine (brand name Cognex);
Donepezil (brand name Aricept);
Rivastigmine (brand name Exelon);
Galantamine (brand name Reminyl).

They have been approved by the FDA for use in treating Alzheimer's disease. All produce some limited improvement in the cognitive symptoms associated with Alzheimer's disease, though they do not slow or halt the progression of the disease. The beneficial effects are typically modest and temporary. Tacrine can also produce severe side-effects including liver damage. Several other cholinesterase inhibitors, including physostigmine, rivastigmine and metrifonate, are currently under investigation by the FDA to see if they can produce reliable improvements in AD symptoms without undue side effects.

Further reading:

Krall WJ, Sramek JJ, Cutler NR (1999) Cholinesterase inhibitors: a therapeutic strategy for Alzheimer disease. Annals of Pharmacotherapy, 33(4):441-50.

Also check the NIH website (http://www.medlineplus.gov) for the most current details about these and other drugs currently under development.