A muscarinic receptor agonist is an agent that activates the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, labelled M1-M5, allowing for further differentiation.
Clinical significance 1
- M1 1.1
- M3 1.2
- Muscarinic versus nicotinic activity 2
- Muscarinic Acetylcholine Receptor Subtypes 3
- See also 4
- References 5
- External links 6
M1-type muscarinic acetylcholine receptors play a role in cognitive processing. In Alzheimer 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.
In the form of pilocarpine, muscarinic receptor agonists have been used medically for a short time.
- Aceclidine, for glaucoma.
- Arecoline, an alkaloid present in the Betel nut.
- Pilocarpine is a drug that acts as a muscarinic receptor agonist that is used to treat glaucoma.
- Cevimeline (AF102B) (Evoxac) is a muscarinic agonist that is an Food and Drug Administration (FDA)-approved drug and used for the management of dry mouth in Sjögren's syndrome.
Muscarinic versus nicotinic activity
|Comparison of cholinergic agonists |
|Carbachol||++||+++||-||Used in the treatment of glaucoma|
|Methacholine||+++||+||++||Used to diagnose bronchial hyperreactivity, a hallmark of asthma and COPD.|
|Bethanechol||+++||-||-||Used in bladder and gastrointestinal hypotonia.|
|Muscarine||+++||-||-||Natural alkaloid found in certain mushrooms. Cause of mushroom poisoning|
|Nicotine||-||+++||-||Natural alkaloid found in the tobacco plant.|
|Pilocarpine||++||-||-||Used in glaucoma.|
|Oxotremorine||++||-||-||Used in research to induce symptoms of Parkinson's disease.|
Muscarinic Acetylcholine Receptor SubtypesThe targets for Muscarinic agonists include the following receptors:
- Fisher A, Brandeis R, Bar-Ner RH, Kliger-Spatz M, Natan N, Sonego H, Marcovitch I, Pittel Z. AF150(S) and AF267B: M1 muscarinic agonists as innovative therapies for Alzheimer's disease. J Mol Neurosci. 2002 Aug-Oct;19(1-2):145-53. PMID 12212772
- Fisher A. M1 muscarinic agonists: Their potential in treatment and as disease-modifying agents in Alzheimer's disease Drug Dev. Res. 50:291-297, 2000. 
- Fisher A (July 2008). "Cholinergic treatments with emphasis on m1 muscarinic agonists as potential disease-modifying agents for Alzheimer's disease".
- Shekhar A, Potter WZ, Lightfoot J, et al. (July 2008). "Selective Muscarinic Receptor Agonist Xanomeline as a Novel Treatment Approach for Schizophrenia". Am J Psychiatry 165 (8): 1033–9.
- Sellin AK, Shad M, Tamminga C. (November 2008). "Muscarinic agonists for the treatment of cognition in schizophrenia". CNS Spectrums 13 (1): 985–96.
- Unless else specified in boxes, then reference is: Table 10-3 in: Rod Flower; Humphrey P. Rang; Maureen M. Dale; Ritter, James M. (2007). Rang & Dale's pharmacology. Edinburgh: Churchill Livingstone.
- Birnbaum S, Barreiro TJ (June 2007). "Methacholine challenge testing: identifying its diagnostic role, testing, coding, and reimbursement". Chest 131 (6): 1932–5.
- Muscarinic Agonists at the US National Library of Medicine Medical Subject Headings (MeSH)