Muscarinic agonist
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.
Contents
Clinical significance
M1
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.[1][2][3]
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 agent xanomeline has been proposed as a potential treatment for schizophrenia.[4][5]
M3
In the form of pilocarpine, muscarinic receptor agonists have been used medically for a short time.
- M3 agonists
- 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 [6] | ||||
|---|---|---|---|---|
| Substance | Receptor specificity | Hydrolysis by acetylcholinesterase |
Comments | |
| Muscarinic | Nicotinic | |||
| Choline | +++ | +++ | ++ | Essential nutrient |
| Acetylcholine | +++ | +++ | +++ | Endogenous ligand |
| Carbachol | ++ | +++ | - | Used in the treatment of glaucoma |
| Methacholine | +++ | + | ++ | Used to diagnose bronchial hyperreactivity,[7] a hallmark of asthma and COPD. |
| Bethanechol | +++ | - | - | Used in bladder and gastrointestinal hypotonia. |
| Muscarine | +++ | - | - | Natural alkaloid found in certain mushrooms. Cause of one form of mushroom poisoning |
| Nicotine | - | +++ | - | Natural alkaloid found in the tobacco plant. |
| Pilocarpine | ++ | - | - | Used in glaucoma. |
| Oxotremorine | ++ | +[8] | - | Used in research to induce symptoms of Parkinson's disease. |
Muscarinic Acetylcholine Receptor Subtypes
The targets for Muscarinic agonists include the following receptors:
| Receptor/Transporter Protein |
|---|
| M1 |
| M2 |
| M3 |
| M4 |
| M5 |
See also
References
- ↑ 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. [1]
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External links
- Muscarinic Agonists at the US National Library of Medicine Medical Subject Headings (MeSH)
