The Core Mechanism of Action: Muscarinic Receptor Agonism
As a parasympathomimetic agent, pilocarpine mimics acetylcholine to stimulate the parasympathetic nervous system. It specifically binds to and activates muscarinic acetylcholine receptors (mAChR), of which there are five subtypes (M1-M5) found in various tissues. This activation increases parasympathetic activity.
Targeting Key Muscarinic Receptor Subtypes
Pilocarpine activates all five muscarinic receptor subtypes, but its most clinically relevant effects are primarily mediated by the M3 receptor subtype. M3 receptors are excitatory and located on exocrine glands and smooth muscles. Activating M3 receptors in glands increases fluid secretion, while activating them in smooth muscles causes contraction. While pilocarpine also affects M1 receptors in the central nervous system, its peripheral M3 actions are most significant for its therapeutic uses.
Effects on Ocular Structures
Pilocarpine's action on muscarinic receptors in the eye is beneficial for treating glaucoma and presbyopia.
Treating Glaucoma
Pilocarpine eye drops constrict the iris sphincter muscle and the ciliary muscle. Ciliary muscle contraction pulls on the scleral spur, increasing tension on the trabecular meshwork. This opens the drainage angle, improving the outflow of aqueous humor and reducing intraocular pressure (IOP), which is the main goal in treating open-angle glaucoma.
Addressing Presbyopia
Pilocarpine eye drops are also used for presbyopia, the age-related loss of near vision. By constricting the pupil (miosis), pilocarpine utilizes the 'pinhole effect,' which increases the depth of focus and improves near vision. Its action on the ciliary muscle also contributes to better near vision.
Effects on Secretory Glands
Oral pilocarpine stimulates exocrine glands like salivary and lacrimal glands, providing relief for impaired gland function.
Treating Dry Mouth (Xerostomia)
Pilocarpine activates M3 receptors on salivary gland cells, leading to increased saliva production. It is a primary treatment for xerostomia caused by Sjögren's syndrome or radiation therapy.
Increasing Tear Production
Stimulation of lacrimal glands by pilocarpine increases tear secretion. Oral administration can improve dry eye symptoms, especially in Sjögren's syndrome patients.
Clinical Applications and Therapeutic Considerations
Understanding pilocarpine's receptor targets guides its use in various medical fields. Topical administration focuses on ocular effects, while oral administration provides more systemic effects. Once a primary glaucoma treatment, it's now also used for presbyopia due to newer formulations.
Comparison of Pilocarpine's Clinical Applications
{Link: NCBI Bookshelf https://www.ncbi.nlm.nih.gov/books/NBK548815/}
Adverse Effects Related to Broad Parasympathetic Stimulation
Oral pilocarpine can cause systemic side effects due to broad cholinergic stimulation.
Conclusion
Pilocarpine primarily acts on muscarinic acetylcholine receptors, especially the M3 subtype, stimulating the parasympathetic nervous system. This action benefits ocular smooth muscles for glaucoma and presbyopia and exocrine glands for dry mouth and dry eyes. Understanding pilocarpine's targets is crucial for proper use and managing potential systemic side effects.
Visit the DrugBank entry for Pilocarpine for more pharmacological details
