Progress in acetylcholinesterase inhibitors for Alzheimer's disease

Current pharmacotherapy of Alzheimer's disease (AD) involves drugs that are known as acetylcholinesterase inhibitors (AChEIs), which increase the acetylcholine concentration in the brain. Although effective in improving cognitive, behavioural and functional impairments, these drugs are not able to alter disease progression. In this review, the recent patent literature on AChEIs from 2002 to early 2005 will be discussed, focusing attention on the novel analogues of the approved drugs, as well as on the most important AD therapeutic advances. The clinical efficacy of AChEIs will probably be enhanced by their combination with other drugs acting through different pharmacological mechanisms. As the neuronal loss comprises more than the forebrain cholinergic system, the weak effectiveness of AChEIs is not surprising. Besides the 'cholinergic hypothesis' approaches, new treatments are emerging based on multipotent compounds able to target the underlying pathogenic mechanisms of AD; these treatments are summarised herein.