M1 agonists as a potential disease-modifying therapy for Alzheimer's disease

Curr Alzheimer Res. 2009 Apr;6(2):112-7. doi: 10.2174/156720509787602915.


Cholinergic deficit is a cardinal feature of Alzheimer's disease, and cholinesterase inhibitors represent one of the most prominent means of mitigating this dysfunction. Cholinesterase inhibitors provide mild symptomatic relief, although they lose their efficacy over time most likely because they are not disease-modifying agents. An alternative strategy for restoring cholinergic function and attenuating the cognitive decline involves acting on the receptors on which acetylcholine acts. Stimulation of muscarinic acetylcholine receptors and in particular the M1 subtype has been shown to have a beneficial effect in restoring cognition in patients with Alzheimer's disease and in attenuating Abeta and tau pathology in different animal models. In this review, we discuss the role of M1 agonists as a potential disease-modifying therapy for Alzheimer's disease.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Animals
  • Antipsychotic Agents / therapeutic use*
  • Humans
  • Models, Biological
  • Muscarinic Agonists / therapeutic use*
  • Receptor, Muscarinic M1 / agonists*
  • Receptor, Muscarinic M1 / metabolism
  • Signal Transduction


  • Antipsychotic Agents
  • Muscarinic Agonists
  • Receptor, Muscarinic M1