Acetyl CoA
+
Choline 
M receptor
N receptor
Primary Strategy for increasing cholinergic
function: block acetylcholinesterase
ACh
Presynaptic nerve terminal
Postsynaptic
nerve terminal
 CAT
Acetylcholinesterase
Choline +
acetate
Acetylcholine (ACh)
AChEI
(donepezil,
rivastigmine
galantamine)
AChEI = acetylcholinesterase inhibitors
Component title: Strategies for increasing cholinergic function: AChEIs
Description: AChE inhibitors are the only modern agents approved for the treatment of AD, and have represented the most promising therapeutic approach to date. The AChE enzyme is responsible for breaking down ACh in the synaptic cleft. By inhibiting this enzyme, AChE inhibitors increase the level of ACh available in the synaptic cleft to stimulate cholinergic receptors, and thus enhance cholinergic function (Francis et al., 1999; Nordberg 1998). Despite different pharmacological profiles, there appears to be little difference between conventional (single-mechanism) AChE inhibitors, such as donepezil, rivastigmine and tacrine, in terms of their effects on clinical measures such as ADAS-COG (Nordberg and Svensson, 1998).
These treatments clearly improve symptoms, but there is uncertainty that these drugs show long-term efficacy and consistency of results between trials (Flicker, 1999).