What is the mechanism of action of pilocarpine?

October 7, 2025 •

2 min read

Derived from the South American plant genus Pilocarpus, pilocarpine has been used to treat glaucoma for over 100 years. It is a direct-acting cholinergic agonist used to increase secretions and promote smooth muscle contraction. So, what is the mechanism of action of pilocarpine? It primarily stimulates muscarinic receptors within the parasympathetic nervous system.

Quick Summary

Pilocarpine is a muscarinic receptor agonist that mimics acetylcholine, stimulating cholinergic receptors to increase exocrine secretions and cause smooth muscle contraction. Its primary therapeutic effects include lowering intraocular pressure by facilitating aqueous humor drainage and increasing salivary flow in patients with dry mouth.

Key Points

Muscarinic Agonist: Pilocarpine is a direct-acting parasympathomimetic that activates muscarinic acetylcholine receptors, mimicking the neurotransmitter acetylcholine.
M3 Receptor Activation: The drug's key effects are mediated primarily by the M3 receptor subtype, which is abundant in the eye's smooth muscles and exocrine glands.
Ocular Pressure Reduction: In the eye, pilocarpine contracts the ciliary muscle and iris sphincter, which opens the trabecular meshwork to increase aqueous humor outflow and lower intraocular pressure.
Increased Salivation: When used for xerostomia, pilocarpine stimulates muscarinic receptors on salivary gland acinar cells to dramatically increase salivary secretion.
Cellular Signaling Cascade: Pilocarpine's binding to M3 receptors triggers the Gq protein pathway, leading to increased intracellular calcium, which is the final signal for contraction and secretion.
Improved Near Vision: Pilocarpine helps treat presbyopia by causing the ciliary muscle to contract, thickening the lens and increasing the depth of focus for clearer near vision.
Widespread Cholinergic Effects: The non-selective nature of pilocarpine means its action can cause widespread parasympathetic side effects, such as increased sweating, flushing, and nausea.

Cellular and Subtype Specificity

Pilocarpine activates muscarinic receptors (M1–M5), but its main effects come from stimulating the M3 subtype. M3 receptors are common in smooth muscles of the eye and in glands such as salivary, sweat, and tear glands. When pilocarpine binds to M3 receptors, it activates a Gq-protein pathway, leading to the production of $IP_3$ and $DAG$. This process increases intracellular calcium, which causes smooth muscle contraction and glandular secretion.

Ocular Effects: Glaucoma and Presbyopia

Pilocarpine's action in the eye is key for treating glaucoma and presbyopia.

Contraction of the Iris Sphincter Muscle

Pilocarpine makes the iris sphincter muscle contract, causing the pupil to become smaller (miosis). This can help in conditions like acute angle-closure glaucoma by opening the drainage angle of the eye.

Contraction of the Ciliary Muscle

Contraction of the ciliary muscle is a significant effect of pilocarpine.

Glaucoma: This contraction pulls on the scleral spur, which opens the trabecular meshwork. This increases the flow of fluid out of the eye, reducing intraocular pressure (IOP).
Presbyopia: Ciliary muscle contraction also changes the shape and position of the eye's lens. This enhances the eye's depth of focus, improving near vision for people with age-related blurry near vision.

Glandular Effects: Xerostomia

In addition to eye treatments, pilocarpine is used orally to treat dry mouth (xerostomia), which can be caused by radiotherapy or Sjögren's syndrome.

Stimulation of Exocrine Glands

When taken by mouth, pilocarpine stimulates muscarinic receptors, mainly M3, on salivary gland cells. This results in a large increase in saliva production.

Comparison with Other Cholinergic Drugs

Pilocarpine's actions and side effects differ from other cholinergic medications like cevimeline (for dry mouth) and bethanechol (for urinary retention).


Feature	Pilocarpine	Bethanechol	Cevimeline
Primary Use	Dry mouth (xerostomia), glaucoma, presbyopia	Urinary retention	Dry mouth (xerostomia)
Receptor Action	Non-selective muscarinic agonist (primary M3 effects)	Primarily muscarinic agonist (M3, M2)	Selective muscarinic agonist (M3)
Adverse Effects	Sweating, flushing, nausea, vision changes, headache	Gastrointestinal upset, urinary frequency, flushing, bradycardia	Sweating, nausea, flushing, diarrhea
Route of Administration	Oral (tablets), Ophthalmic (drops)	Oral (tablets)	Oral (capsules)

Signal Transduction Pathway

The signaling pathway for pilocarpine involves these key steps:

Receptor Binding: Pilocarpine binds to M3 muscarinic receptors.
Gq Protein Activation: This activates a Gq-protein.
PLC Stimulation: The Gq-protein activates PLCβ.
PIP2 Hydrolysis: PLCβ breaks down PIP2 into $IP_3$ and $DAG$.
Calcium Release: $IP_3$ causes calcium to be released from storage inside the cell.
Physiological Response: Increased calcium leads to effects like muscle contraction or gland secretion.

Conclusion

Pilocarpine works by stimulating muscarinic receptors, like acetylcholine, to increase intracellular calcium. This action causes smooth muscles to contract and glands to secrete fluids. This mechanism makes it useful for treating conditions such as glaucoma, presbyopia, and dry mouth.

Visit a resource for further information on cholinergic pharmacology.

Frequently Asked Questions

Pilocarpine constricts the pupil and contracts the ciliary muscle. This action pulls on the trabecular meshwork, opening up its pores and increasing the drainage of aqueous humor, which lowers the pressure inside the eye.

Muscarinic receptors are the primary targets for pilocarpine. The drug binds directly to these receptors, particularly the M3 subtype, to trigger the same physiological responses as acetylcholine in the parasympathetic nervous system.

Yes, oral pilocarpine can improve symptoms of dry eye, such as those associated with Sjögren's syndrome, by stimulating lacrimal glands to increase tear production. However, topical application may sometimes cause meibomian gland dysfunction, potentially worsening dry eye.

The fundamental mechanism (muscarinic receptor agonism) is the same, but the effects depend on the target tissue. In the eye, it causes muscle contraction to reduce pressure or improve near vision. In the mouth, it stimulates glandular secretion to produce saliva.

Due to its systemic cholinergic effects, common side effects include increased sweating, flushing, nausea, diarrhea, headaches, and visual changes like blurred or dim vision.

For presbyopia, pilocarpine eye drops cause contraction of the ciliary muscle and pupil. The ciliary muscle contraction thickens the lens, while pupil constriction increases the depth of focus, collectively improving near vision.

Research suggests pilocarpine can have varying effects depending on the cell type and receptor expression levels. For example, while it is a full agonist for overexpressed M3 receptors in some cell lines, studies show it acts as an antagonist for endogenous M3 receptors under certain conditions, indicating a potential signaling bias.