A muscarinic receptor agonist is an agent that enhances the activity of the muscarinic acetylcholine receptor

Muscarinic acetylcholine receptor

Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...

. The muscarinic receptor has different subtypes, labelled M1-M5, allowing for further differentiation.

M1

M1-type muscarinic acetylcholine receptors play a role in cognitive

Cognition

In science, cognition refers to mental processes. These processes include attention, remembering, producing and understanding language, solving problems, and making decisions. Cognition is studied in various disciplines such as psychology, philosophy, linguistics, and computer science...

 processing. In Alzheimer disease (AD) amyloid

Amyloid

Amyloids are insoluble fibrous protein aggregates sharing specific structural traits. Abnormal accumulation of amyloid in organs may lead to amyloidosis, and may play a role in various neurodegenerative diseases.-Definition:...

 formation may decrease the ability of these receptors to transmit signals leading to decrease 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

Neurotrophin

Neurotrophins are a family of proteins that induce the survival, development, and function of neurons.They belong to a class of growth factors, secreted proteins that are capable of signaling particular cells to survive, differentiate, or grow. Growth factors such as neurotrophins that promote the...

, decrease amyloid depositions, and improve damage due to oxidative stress

Oxidative stress

Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...

. Tau

Tau

Tau is the 19th letter of the Greek alphabet. In the system of Greek numerals it has a value of 300.The name in English is pronounced , but in modern Greek it is...

-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

Xanomeline

Xanomeline is a muscarinic acetylcholine receptor agonist with reasonable selectivity for the M1 and M4 subtypes, though it is also known to act as a M5 receptor antagonist...

 has been proposed as a potential treatment for schizophrenia

Schizophrenia

Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

.

M3

In the form of pilocarpine

Pilocarpine

Pilocarpine is a parasympathomimetic alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist in the parasympathetic nervous system, which acts therapeutically at the muscarinic acetylcholine receptor M3 due to its...

, muscarinic receptor agonists have been used medically for a long time.

• M3 agonists
  • Aceclidine
    Aceclidine
    Aceclidine is a parasympathomimetic miotic agent used in the treatment of narrow angle glaucoma. It decreases intraocular pressure.- Adverse effects :...
    
    , for glaucoma.
  • Arecoline
    Arecoline
    Arecoline is an alkaloid natural product found in the areca nut, the fruit of the areca palm . It is an odourless oily liquid volatile in steam, miscible with most organic solvents and water, but extractable from the latter by ether in presence of dissolved salts. The salts are crystalline, but...
    
    , an alkaloid present in the Betel nut
    Betel nut
    The Areca nut is the seed of the Areca palm , which grows in much of the tropical Pacific, Asia, and parts of east Africa. It is commonly referred to as "betel nut" as it is often chewed wrapped in betel leaves.-Description:...
    
    .
  • Pilocarpine
    Pilocarpine
    Pilocarpine is a parasympathomimetic alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist in the parasympathetic nervous system, which acts therapeutically at the muscarinic acetylcholine receptor M3 due to its...
    
    is a drug that acts as a muscarinic receptor agonist that is used to treat glaucoma
    Glaucoma
    Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
    
    .
  • Cevimeline (AF102B) (Evoxac™) is a muscarinic agonist that is an Food and Drug Administration
    Food and Drug Administration
    The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
    
     (FDA)-approved drug
    Approved drug
    In the United States, the FDA approves drugs. Before a drug can be prescribed, it must undergo an extensive FDA approval process. This process involves first testing the drug on animals or in medical labs. If found to be safe by the FDA and approved for the next phase of study, the drug is then...
    
     and used for the management of dry mouth in Sjögren's syndrome
    Sjögren's syndrome
    Sjögren's syndrome , also known as "Mikulicz disease" and "Sicca syndrome", is a systemic autoimmune disease in which immune cells attack and destroy the exocrine glands that produce tears and saliva....
    
    .

Muscarinic versus nicotinic activity

Muscarinic agonists
Drug	Receptor specificity		Hydrolysis by acetylcholinesterase Acetylcholinesterase "Acetylcholinesterase, also known as AChE or acetylcholine acetylhydrolase, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic nervous system, where its activity serves to terminate...	Comments
	Muscarinic	Nicotinic
Acetylcholine Acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...	+++	+++	+++
Carbachol Carbachol Carbachol , also known as carbamylcholine, is a drug that binds and activates the acetylcholine receptor. Thus it is classified as a cholinergic agonist. It is primarily used for various ophthalmic purposes, such as for treating glaucoma, or for use during ophthalmic surgery...	++	+++	-
Methacholine	+++	+	++
Bethanechol Bethanechol Bethanechol is a parasympathomimetic choline carbamate that selectively stimulates muscarinic receptors without any effect on nicotinic receptors. Unlike acetylcholine, bethanechol is not hydrolyzed by cholinesterase and will therefore have a long duration of action. Bethanechol does not involve...	+++	-	-	Used in bladder and gastrointestinal hypotonia.
Muscarine Muscarine Muscarine, L--muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species, such as the deadly C. dealbata. Mushrooms in the genera Entoloma and Mycena have also been found to contain levels of muscarine which can be dangerous if ingested...	+++	-	-	Cause of mushroom poisoning
Pilocarpine Pilocarpine Pilocarpine is a parasympathomimetic alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist in the parasympathetic nervous system, which acts therapeutically at the muscarinic acetylcholine receptor M3 due to its...	++	-	-	Used in glaucoma
Oxotremorine Oxotremorine Oxotremorine is a cholinomimetic that acts as a non-selective muscarinic acetylcholine receptor agonist.Oxotremorine produces ataxia, tremor and spasticity, similar to those symptoms seen in Parkinsonism, and has thus become a research tool in experimental studies aimed at determining more...	++	-	-