Cholinesterase Inhibitors

An Overview

Patients with AD have reduced production of choline acetyltransferase, which leads to diminished acetylcholine production and alterations in cognitive functioning.

Drug development in AD has largely focused on medications that increase levels of acetylcholine in the CNS. Early research with acetylcholine precursors was largely unsuccessful. Researchers then turned from attempting to increase acetylcholine synthesis to developing compounds that would inhibit its breakdown in the synapse. Cholinesterase inhibitors (CHE-I) were the first class of drugs to demonstrate utility in AD clinical trials.

Tacrine (Cognex) was the first compound of this class to be approved for the treatment of mild-moderate AD in 1993, followed by donepezil (Aricept) in 1996, and recently rivastigmine (Exelon) in June 2000. The approval of tacrine was an important landmark in the history of AD research, transforming AD into a treatable illness.

Most recently (March 2001), galantamine (previously Reminyl™ now Razadyne ER™), has been added to the list of FDA approved drugs for treatment of mild to moderately severe AD.