What are Cholinergic Drugs? Understanding Parasympathomimetics

October 8, 2025 •

4 min read

The human body's 'rest and digest' functions are primarily controlled by the parasympathetic nervous system, with acetylcholine being its chief neurotransmitter. Cholinergic drugs are a class of medications that target this system by enhancing or mimicking the action of acetylcholine. This article explains what these drugs are, their mechanisms, and their important therapeutic applications.

Quick Summary

Cholinergic drugs enhance the activity of the neurotransmitter acetylcholine to increase parasympathetic nervous system functions. They are categorized as direct-acting agents, which mimic acetylcholine, or indirect-acting agents, which inhibit its breakdown. Therapeutic uses include treating Alzheimer's disease, myasthenia gravis, glaucoma, and urinary retention.

Key Points

Enhance Acetylcholine: Cholinergic drugs boost the activity of acetylcholine, the main neurotransmitter of the 'rest and digest' parasympathetic nervous system.
Two Mechanisms: They can act directly by mimicking acetylcholine at receptors or indirectly by inhibiting the enzyme that breaks it down.
Treat Alzheimer's: Indirect-acting cholinesterase inhibitors like donepezil are a primary treatment for mild to moderate Alzheimer's disease to address cognitive decline.
Manage Myasthenia Gravis: Pyridostigmine, another cholinesterase inhibitor, helps improve muscle strength in patients with myasthenia gravis.
Relieve Glaucoma: Direct-acting agonists like pilocarpine are used to reduce high intraocular pressure in glaucoma by improving fluid drainage.
Side Effects are Parasympathetic: Common side effects result from widespread parasympathetic overstimulation, including nausea, diarrhea, increased sweating, and a slow heart rate.
Opposite of Anticholinergics: Cholinergic drugs have opposing effects to anticholinergic drugs, which block acetylcholine activity and are used for different conditions like overactive bladder.

What is a cholinergic drug?

Cholinergic drugs, also known as parasympathomimetics, are a class of pharmaceutical agents that increase the activity of the neurotransmitter acetylcholine (ACh). Acetylcholine is the key chemical messenger for the parasympathetic nervous system, which controls involuntary bodily functions during periods of rest, such as slowing the heart rate, increasing digestion, and regulating glandular secretions.

By augmenting the effects of acetylcholine, these drugs essentially shift the body's balance towards a "rest and digest" state. This can be achieved through two primary mechanisms: either by mimicking acetylcholine's action directly or by blocking the enzyme responsible for its breakdown. Cholinergic drugs interact with two main types of cholinergic receptors: muscarinic and nicotinic receptors, which are located throughout the central and peripheral nervous systems.

Types of cholinergic drugs

Cholinergic drugs are generally divided into two main categories based on their mechanism of action.

Direct-acting cholinergic agonists

These drugs bind directly to and activate cholinergic receptors, thereby mimicking the effects of acetylcholine. They are often used for specific, localized actions. Examples include:

Choline esters: This includes drugs like bethanechol and carbachol. Bethanechol is a muscarinic agonist used to stimulate bladder emptying in patients with urinary retention. Carbachol and other choline esters are sometimes used in ophthalmology.
Alkaloids: Pilocarpine, an alkaloid, is commonly used as eye drops to treat glaucoma by causing pupillary constriction and increasing the outflow of aqueous humor. It can also be used orally to treat dry mouth (xerostomia).
Cevimeline: Another muscarinic agonist used for treating dry mouth associated with Sjögren's syndrome.

Indirect-acting cholinergic agents (Cholinesterase Inhibitors)

Instead of acting on receptors, these agents work by inhibiting acetylcholinesterase, the enzyme that breaks down acetylcholine in the synapse. This causes acetylcholine to accumulate and have a prolonged effect on its receptors. These inhibitors are further classified as either reversible or irreversible.

Reversible inhibitors: These are often used therapeutically and have a moderate duration of action.
- Donepezil, Rivastigmine, Galantamine: Primarily used to treat cognitive and behavioral symptoms of mild to moderate Alzheimer's disease by increasing acetylcholine availability in the brain.
- Pyridostigmine: The drug of choice for managing myasthenia gravis, a disorder characterized by muscle weakness, by prolonging acetylcholine's action at the neuromuscular junction.
Irreversible inhibitors: These bind to acetylcholinesterase permanently, with prolonged effects lasting until new enzyme molecules are synthesized. This category includes highly toxic organophosphate compounds used as insecticides or nerve agents, such as sarin and malathion. The therapeutic use is very limited due to their high toxicity.

Clinical applications of cholinergic drugs

Cholinergic medications are used to manage a variety of medical conditions by leveraging their effects on different parts of the body. Key therapeutic uses include:

Alzheimer's Disease: The mainstay of treatment for mild-to-moderate Alzheimer's disease is the use of cholinesterase inhibitors like donepezil, rivastigmine, and galantamine to boost acetylcholine levels in the brain and improve cognitive function.
Myasthenia Gravis: Pyridostigmine is used to increase acetylcholine at the neuromuscular junction, which helps improve muscle strength in patients with this autoimmune disorder.
Glaucoma: Pilocarpine eye drops are a third-choice drug used to treat open-angle glaucoma by constricting the pupil and increasing aqueous humor outflow to lower intraocular pressure.
Urinary Retention: Bethanechol is used to stimulate bladder muscle contraction and promote urination in cases of non-obstructive urinary retention after surgery or childbirth.
Dry Mouth (Xerostomia): Pilocarpine and cevimeline can increase saliva production in patients suffering from severe dry mouth, such as those with Sjögren's syndrome.

Side effects and contraindications

Because cholinergic drugs broadly stimulate the parasympathetic nervous system, they can cause significant side effects that result from the overstimulation of various organs.

Common Side Effects: These can include gastrointestinal issues such as nausea, vomiting, diarrhea, and abdominal cramping. Other effects are increased sweating, salivation, lacrimation, and constricted pupils leading to blurred vision.
Cardiovascular Effects: These drugs can cause a lowered heart rate (bradycardia) and decreased blood pressure (hypotension).
Contraindications: Cholinergic drugs are generally avoided in patients with conditions like asthma or chronic obstructive pulmonary disease (COPD) due to the risk of bronchoconstriction, urinary or gastrointestinal tract obstruction, bradycardia, or coronary artery disease.

Cholinergic vs. Anticholinergic drugs

It is helpful to contrast cholinergic drugs with their functional opposites, anticholinergic drugs, to fully understand their effects.


Feature	Cholinergic Drugs	Anticholinergic Drugs
Mechanism	Enhance or mimic acetylcholine activity.	Block the action of acetylcholine at its receptors.
Effect on PNS	Stimulate the parasympathetic nervous system.	Inhibit the parasympathetic nervous system.
Heart Rate	Decreases heart rate (bradycardia).	Increases heart rate (tachycardia).
Gastrointestinal	Increases motility and secretions, causing cramping, diarrhea.	Decreases motility and secretions, causing constipation and dry mouth.
Pupils	Constricts pupils (miosis).	Dilates pupils (mydriasis).
Secretions	Increases salivation, sweating, and tear production.	Decreases salivation, sweating, and tear production.
Clinical Uses	Alzheimer's, myasthenia gravis, glaucoma.	COPD, overactive bladder, Parkinson's symptoms.

Conclusion

Cholinergic drugs play a vital role in modern medicine, providing targeted therapies for a range of conditions by manipulating the body's acetylcholine levels and activity. From improving muscle strength in myasthenia gravis and managing intraocular pressure in glaucoma to addressing cognitive decline in Alzheimer's disease, their effects are diverse and clinically significant. However, their broad influence on the parasympathetic nervous system requires careful use, as evidenced by a range of potential side effects. Understanding the distinction between direct and indirect mechanisms is key to appreciating their therapeutic applications and risk profiles. For a comprehensive list of specific medications and their properties, the National Center for Biotechnology Information provides valuable information.

Frequently Asked Questions

Cholinergic drugs typically slow the heart rate and decrease the force of cardiac muscle contractions by stimulating the parasympathetic nervous system. This effect, known as bradycardia, is a potential side effect.

Yes, some direct-acting cholinergic drugs like pilocarpine and cevimeline are used to treat dry mouth, or xerostomia. They work by stimulating exocrine glands, including the salivary glands, to increase saliva production.

Direct-acting cholinergic drugs bind directly to and activate acetylcholine receptors, mimicking the neurotransmitter. Indirect-acting drugs, also called cholinesterase inhibitors, block the enzyme that breaks down acetylcholine, thus increasing its concentration in the synapse.

Common side effects include increased salivation, sweating, and tear production, nausea, vomiting, diarrhea, abdominal cramps, blurred vision, dizziness, and a slow heart rate. These effects are due to overstimulation of the parasympathetic system.

Myasthenia gravis is an autoimmune disease causing muscle weakness. Cholinergic drugs, specifically indirect-acting cholinesterase inhibitors like pyridostigmine, increase the amount of acetylcholine at the neuromuscular junction, which enhances muscle contraction and improves muscle strength.

Yes, direct-acting cholinergic agents such as pilocarpine and carbachol are used as miotic eye drops to treat open-angle glaucoma. They cause the pupil to constrict, which improves the outflow of aqueous humor and lowers intraocular pressure.

A cholinergic crisis is a medical emergency caused by an overdose of a cholinergic drug. It involves excessive parasympathetic stimulation, leading to severe symptoms such as circulatory collapse, low blood pressure, shock, bloody diarrhea, and cardiac arrest. Atropine is an antidote for this condition.

Anticholinergic drugs block acetylcholine receptors, producing effects opposite to cholinergic drugs. Administering both can neutralize their therapeutic effects and is not advised. Careful medical consideration is required to manage conditions where one or both drug classes may be involved.