The Second Generation of Cholinesterase Inhibitors: Clinical and Pharmacological Effects

Abstract

One potentially important and widely studied approach to cholinomimetic therapy in Alzheimer disease (AD) is the use of substances that inhibit acetylcholinesterase (AChE). Acetylcholinesterase is the enzyme that inactivates acetylcholine (ACh) and thereby terminates the activity of the neurotransmitter. The rationale of the use of acetylcholinesterase inhibitors in AD is based on the finding that the loss of cholinergic neuronal function results in a deficiency in ACh concentrations in the CNS (Whitehouse et al., 1981; Struble et al., 1982; Coyle et al., 1983; Arendt et al., 1985). This can be regarded as a relative overactivity of AChE. AChE inhibitors reduce AChE activity and increase the duration of survival of released ACh (Giacobini 1991). The increased concentration of ACh can then stimulate the post synaptic cellular matrix, which is regarded as being relatively more intact in AD (Whitehouse et al., 1981).KeywordsAlzheimer DiseaseAChE ActivityAChE InhibitionSenile DementiaAlzheimer Disease PatientThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.