Neurotherapeutics

, Volume 5, Issue 3, pp 433–442

Cholinergic treatments with emphasis on M1 muscarinic agonists as potential disease-modifying agents for Alzheimer’s disease

Review Article

DOI: 10.1016/j.nurt.2008.05.002

Cite this article as:
Fisher, A. Neurotherapeutics (2008) 5: 433. doi:10.1016/j.nurt.2008.05.002

Summary

The only prescribed drugs for treatment of Alzheimer’s disease (AD) are acetylcholinesterase inhibitors (e.g., donepezil, rivastigmine, galantamine, and tacrine) and memantine, an NMDA antagonist. These drugs ameliorate mainly the symptoms of AD, such as cognitive impairments, rather than halting or preventing the causal neuropathology. There is currently no cure for AD and there is no way to stop its progression, yet there are numerous therapeutic approaches directed against various pathological hallmarks of AD that are extensively being pursued. In this context, the three major hallmark characteristics of AD (i.e., the CNS cholinergic hypofunction, formation of β-amyloid plaques, and tangles containing hyperphosphorylated tau proteins) are apparently linked. Such linkages may have therapeutic implications, and this review is an attempt to analyze these versus the advantages and drawbacks of some cholinergic compounds, such as acetylcholinesterase inhibitors, M1 muscarinic agonists, M2 antagonists, and nicotinic agonists. Among the reviewed treatments, M1 selective agonists emerge, in particular, as potential disease modifiers.

Key Words

Alzheimer’scholinergicβ-amyloidtauacetylcholinesterase inhibitorsM1 muscarinicnicotinicagonistsM2 muscarinic antagonists
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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2008

Authors and Affiliations

  1. 1.Israel Institute for Biological ResearchNess-ZionaIsrael