Muscarinic agonist
activating agent of the muscarinic acetylcholine receptor
A muscarinic acetylcholine receptor agonist, also known as a muscarinic agonist or as a muscarinic agent, is an agent that activates the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, labelled M1-M5, allowing further differentiation.
Clinical significance
M1
M1-type muscarinic acetylcholine receptors play a role in cognitive processing. In Alzheimer's disease (AD), amyloid formation may decrease the ability of these receptors to transmit signals, leading to decreased cholinergic activity. As these receptors themselves appear relatively unchanged in the disease process, they have become a potential therapeutic target when trying to improve cognitive function in patients with AD.
A number of muscarinic agonists have been developed and are under investigation to treat AD. These agents show promise as they are neurotrophic, decrease amyloid depositions, and improve damage due to oxidative stress. Tau-phosphorylation is decreased and cholinergic function enhanced. Notably several agents of the AF series of muscarinic agonists have become the focus of such research:. AF102B, AF150(S), AF267B. In animal models that are mimicking the damage of AD, these agents appear promising.
The dual M1, M4 agonist xanomeline has been proposed as a potential treatment for schizophrenia. Xanomeline/trospium chloride was approved in the US in 2024.
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