Muscarinic agonists: Uses, common brands, and safety info

Muscarinic agonists are drugs that work by activating acetylcholine receptors in the body. Acetylcholine is an essential neurotransmitter involved with the parasympathetic nervous system. Adequate levels of acetylcholine are needed for normal processes in the body, such as digestion, heart rate regulation, urination, memory formation, and learning. Muscarinic agonists can be used to treat glaucoma, Alzheimer’s disease, and urinary retention, among other conditions. 

Continue reading to learn about muscarinic agonists, their different uses, and potential side effects. 

Other muscarinic agonists are cholinergic 

• Pilocar (pilocarpine)

• Provocholine (methacholine)

• Miostat (carbachol)

• Isopto Carbachol (carbachol)

• Enlon (edrophonium)

What are muscarinic agonists?

Muscarinic agonists are cholinergic drugs that stimulate the activity of the parasympathetic nervous system. They can mimic the effects of acetylcholine or increase the available levels of acetylcholine. Acetylcholine can then bind to acetylcholine or cholinergic receptors, which can lead to therapeutic effects for people with certain health conditions. 

Muscarinic agonists can have various effects on the body, depending on the specific drug prescribed. They can help slow heart rate, contract smooth muscle in the urinary and digestive tract, and increase the secretion of saliva, mucus, and gastric acid. They’re generally used to treat conditions like ileus, urinary retention, and Alzheimer’s disease. They can also help increase the outflow of fluid (aqueous humor) from the eye to treat glaucoma and high pressure in the eye.

There are several different cholinergic agonist drugs available, and they may work in different ways. These drugs can be administered as tablets, capsules, inhalation solutions, eye drops, or injections.

How do muscarinic agonists work?

Muscarinic agonists work by stimulating acetylcholine receptors and have parasympathomimetic actions. They are grouped into two different types: direct agonists and indirect agonists. Direct muscarinic agonists act like acetylcholine and bind to acetylcholine receptors. Acetylcholinesterase inhibitors block the acetylcholinesterase enzyme, which is responsible for breaking down acetylcholine. Inhibition of the acetylcholinesterase enzyme can increase levels of acetylcholine to activate acetylcholine receptors. 

Activation of muscarinic receptors

The muscarinic acetylcholine receptors include M1, M2, M3, M4, and M5 receptors. However, muscarinic agonists typically provide therapeutic effects through the muscarinic receptor subtypes M1, M2, and M3. 

The M1 receptor plays a major role in the central nervous system (CNS), and it is linked to memory and learning problems in Alzheimer’s disease. Muscarinic agonists like Aricept (donepezil), Razadyne ER (galantamine), and Exelon (rivastigmine) work as cholinesterase inhibitors to decrease the breakdown of acetylcholine and increase acetylcholine in the synapse. These drugs can help stimulate M1 receptor activation to treat symptoms of Alzheimer’s disease. They may also be combined with other drugs like Aduhelm (aducanumab) to decrease the build-up of amyloid plaques, or brain lesions associated with Alzheimer’s disease. 

The M2 receptor is primarily found in the heart. Muscarinic receptor agonists can activate the M2 receptor to decrease heart rate. 

The M3 receptor is primarily found in the eyes, blood vessels, and smooth muscle of the intestines, bladder, and airways. M3 receptor activation can cause effects like widening of the blood vessels (vasodilation) and contraction of the smooth muscle in the bladder.  

What are muscarinic agonists used for?

Muscarinic agonists are available in different forms and can be used to treat different health conditions. These drugs may have both FDA-approved and off-label indications, which will depend on the specific drug prescribed. Examples of muscarinic agonist uses include the treatment of:  

• Glaucoma 

• Ocular hypertension (high pressure in the eye)

• Xerostomia (dry mouth) associated with Sjogren’s syndrome

• Alzheimer’s disease

• Urinary retention

• Myasthenia gravis

• Neurogenic or postoperative ileus

Ophthalmic drugs like Isopto Carpine (pilocarpine) and Miostat (carbachol) are used to treat eye disorders like glaucoma and ocular hypertension. They help decrease intraocular pressure by contracting the ciliary muscles, which increase the outflow of fluid from the eye. 

Urecholine (bethanechol) is approved to treat urinary retention. It increases bladder emptying by stimulating the contraction of the bladder smooth muscle. 

Salagen (pilocarpine) and Evoxac (cevimeline) are administered as oral drugs to help treat dry mouth associated with Sjogren’s syndrome. They help stimulate the production of saliva in the mouth. 

Consult a healthcare provider for medical advice on the use of muscarinic agonists. 

Who can take muscarinic agonists?

Adults 

Muscarinic agonists are often prescribed to adults for different indications. Drugs like pilocarpine, carbachol, bethanechol, and methacholine are all approved for use in adults. The use of muscarinic agonists in adults will depend on the condition or symptoms being treated. 

Children 

Muscarinic agonists may be used in children for different conditions. Pilocarpine eye drops may be prescribed to children with congenital glaucoma. Some muscarinic agonists may be used off-label in children for conditions like urinary retention. 

Seniors

Alzheimer’s disease is a common neurological disorder in the elderly. Certain muscarinic agonists called cholinesterase inhibitors are beneficial for seniors with cognitive dysfunction. Cholinesterase inhibitors commonly prescribed in older adults with Alzheimer’s disease include Aricept (donepezil), Exelon (rivastigmine), and Razadyne ER (galantamine). 

Older adults may be prone to experiencing certain health conditions that may be contraindicated with certain muscarinic agonists. Older adults with lung disease, peptic ulcer disease, heart disease, or urinary obstruction should use caution with or avoid the use of muscarinic agonists. 

Can you take muscarinic agonists while pregnant or breastfeeding?

There is not enough data on whether muscarinic agonists are completely safe in women who are pregnant or breastfeeding. Drugs administered in the eye are not extensively absorbed throughout the body. Therefore, ocular cholinergic agonists like pilocarpine may be safe for use in women who are pregnant or breastfeeding. 

Caution is advised when considering the use of muscarinic agonists during pregnancy or breastfeeding. Oral and injectable muscarinic agonists may be absorbed throughout the body, which can affect an unborn fetus or breastfeeding child. Consult a healthcare provider on the benefits and risks of using a muscarinic agonist while pregnant or breastfeeding. 

Are muscarinic agonists safe?

Muscarinic agonists are generally safe when taken as prescribed under the guidance of a doctor or healthcare provider. Potential adverse effects will depend on the condition being treated, other medications being taken, and the dosage of the specific drug prescribed. 

Tell your healthcare provider if you have a history one of any of the following before starting treatment with a muscarinic agonist:

• Asthma or chronic obstructive pulmonary disorder (COPD)

• Peptic ulcer disease

• Coronary vascular disease

• Hyperthyroidism

• Bladder and intestinal obstruction

• Eye problems like severe miosis

• Orthostatic hypotension

Acetylcholine toxicity from muscarinic agonists is possible. Toxicity may cause symptoms like diarrhea, excessive urination, bronchospasm, slow heartbeat (bradycardia), increased sweating, vomiting, and abdominal pain. For this reason, muscarinic agonists should only be used with a prescription. 

Black Box Warnings

There are no black box warnings found on the FDA labels of muscarinic agonists

Muscarinic agonist Recalls

Pilocarpine eye drops [March 2019]

Muscarinic agonists restrictions

Muscarinic agonists are not recommended in people with asthma, COPD, peptic ulcer disease, coronary heart disease, or hyperthyroidism. 

Muscarinic agonists can increase mucous secretion and cause constriction of the smooth muscles in the lungs and airways. The use of these drugs may worsen symptoms of respiratory conditions like asthma and COPD. 

People with peptic ulcers should avoid muscarinic receptor agonists or use them with caution. These medications can increase the secretion of acid in the stomach and gastrointestinal tract. Increased levels of acid can worsen symptoms of peptic ulcer disease. 

Muscarinic agonists can cause hypotension and reduced blood flow. People with coronary heart disease may have decreased blood flow caused by cholesterol plaques in the blood vessels. Muscarinic agonists can worsen heart disease and increase the risk of complications.

People with hyperthyroidism are at risk of irregular rhythms (arrhythmias). Muscarinic agonists can cause a slow heart rate and reduced blood pressure, which may indirectly lead to increased levels of norepinephrine. High levels of norepinephrine can increase the risk of arrhythmias in people with hyperthyroidism. 

Are muscarinic agonists controlled substances?

No, muscarinic agonists are not controlled substances. 

Common muscarinic agonists side effects

Common side effects of muscarinic agonists include the following:

• Sweating

• Increased tear production

• Increased urination

• Diarrhea

• Abdominal cramps

• Muscle twitching

• Shrinking of the pupil (miosis)

• Slow heart rate 

• Increased saliva production

• Bronchospasm

• Flushing

More severe but rare side effects include:

• Trouble breathing

• Irregular heart rhythm

• Seizures

Muscarinic agonist side effects depend on the potency and selectivity of the medication prescribed. Side effects are usually mild and temporary when muscarinic agonists are taken as directed. 

When muscarinic receptor agonists are administered in the eye, there is limited absorption into the body. Therefore, the use of ophthalmic muscarinic agonists has a lower risk of serious side effects than the use of oral muscarinic agonists. 

How much do muscarinic agonists cost?

Muscarinic agonists are available in brand and generic formulations. Most Medicare and insurance plans will cover the cost of generic muscarinic agonists. Consult the health insurance plan or pharmacy to determine the exact cost of a supply. Some muscarinic agonists can be expensive without insurance, and the price can vary widely. To help save on the cost of prescription medications, SingleCare offers a prescription discount card.