Pilocarpine

Overview

Pilocarpine is a lactone alkaloid originally extracted from plants of the Pilocarpus genus. It is used as a medication to reduce pressure inside the eye and treat dry mouth. As an eye drop it is used to manage angle closure glaucoma until surgery can be performed, ocular hypertension, primary open angle glaucoma, and to constrict the pupil after dilation. However, due to its side effects, it is no longer typically used for long-term management. Onset of effects with the drops is typically within an hour and lasts for up to a day. By mouth it is used for dry mouth as a result of Sjögren's disease or radiation therapy.[1–7] WP

Common side effects of the eye drops include irritation of the eye, increased tearing, headache, and blurry vision. Other side effects include allergic reactions and retinal detachment. Use is generally not recommended during pregnancy. Pilocarpine is in the miotics family of medication. It works by activating cholinergic receptors of the muscarinic type which cause the trabecular meshwork to open and the aqueous humor to drain from the eye.[2][8][9] WP

Pilocarpine was isolated in 1874 by Hardy and Gerrard and has been used to treat glaucoma for more than 100 years. It is on the World Health Organization's List of Essential Medicines. It was originally made from the South American plant Pilocarpus.[10–13] WP

Drug class

plainlist WP

From the Wikipedia article's infobox.

Uses, dosage and effects

Medical uses

Pilocarpine stimulates the secretion of large amounts of saliva and sweat. It is used to prevent or treat dry mouth, particularly in Sjögren syndrome, but also as a side effect of radiation therapy for head and neck cancer.[14][15] WP

It may be used to help differentiate Adie syndrome from other causes of unequal pupil size.[16][17] WP

It may be used to treat a form of dry eye called aqueous deficient dry eye (ADDE).[18] WP

Surgery

Pilocarpine is sometimes used immediately before certain types of corneal grafts and cataract surgery. It is also used prior to YAG laser iridotomy. In ophthalmology, pilocarpine is also used to reduce symptomatic glare at night from lights when the patient has undergone implantation of phakic intraocular lenses; the use of pilocarpine would reduce the size of the pupils, partially relieving these symptoms. The most common concentration for this use is pilocarpine 1%. Pilocarpine is shown to be just as effective as apraclonidine in preventing intraocular pressure spikes after laser trabeculoplasty.[19][20][21] WP⚠ Wikipedia itself has flagged this text: citation needed.⚠ Wikipedia itself has flagged this text: dubious.

Presbyopia

In 2021, the US Food and Drug Administration (FDA) approved pilocarpine hydrochloride as an eye drop treatment for presbyopia, age-related difficulty with near-in vision. It works by causing the pupils to constrict, increasing depth of field, similar to the effect of pinhole glasses.[22][23] WP

Other

Pilocarpine is used to stimulate sweat glands in a sweat test to measure the concentration of chloride and sodium that is excreted in sweat. It is used to diagnose cystic fibrosis.[24] WP

Risks and side effects

Adverse effects

Use of pilocarpine may result in a range of adverse effects, most of them related to its non-selective action as a muscarinic receptor agonist. Systemic (oral) pilocarpine has been known to cause excessive salivation, sweating, bronchial mucus secretion, bronchospasm, bradycardia, vasodilation, and diarrhea. Eye drops can result in brow ache and chronic use in miosis. It can also cause temporary blurred vision or darkness of vision, temporary shortsightedness, hyphema and retinal detachment. WP

Pharmacology

Pharmacology

Pilocarpine is a drug that acts as a muscarinic receptor agonist. It acts on a subtype of muscarinic receptor (M₃) found on the iris sphincter muscle, causing the muscle to contract – resulting in pupil constriction (miosis). Pilocarpine also acts on the ciliary muscle and causes it to contract. When the ciliary muscle contracts, it opens the trabecular meshwork through increased tension on the scleral spur. This action facilitates the rate that aqueous humor leaves the eye to decrease intraocular pressure. Paradoxically, when pilocarpine induces this ciliary muscle contraction (known as an accommodative spasm) it causes the eye's lens to thicken and move forward within the eye. This movement causes the iris (which is located immediately in front of the lens) to also move forward, narrowing the anterior chamber angle. Narrowing of the anterior chamber angle increases the risk of increased intraocular pressure.[25] WP

Research

Research

Pilocarpine is used to induce chronic epilepsy in rodents, commonly rats, as a means to study the disorder's physiology and to examine different treatments. Smaller doses may be used to induce salivation in order to collect samples of saliva, for instance, to obtain information about IgA antibodies.[26][27] WP

Legal status

Preparation

Plants in the genus Pilocarpus are the only known sources of pilocarpine, and commercial production is derived entirely from the leaves of Pilocarpus microphyllus (Maranham Jaborandi). This genus grows only in South America, and Pilocarpus microphyllus is native to several states in northern Brazil.[28] WP

Pilocarpine is extracted from the leaves of Pilocarpus microphyllus in a multi-step process: the sample is moistened with dilute sodium hydroxide to transform the alkaloid into its free-base form then extracted using chloroform or a suitable organic solvent. Pilocarpine can then be further purified by re-extracting the resulting solution with aqueous sulfuric acid then readjusting the pH to basic using ammonia and a final extraction by chloroform.[29][30][31] WP

It can also be synthesized from 2-ethyl-3-carboxy-2-butyrolactone in an eight-step process from the acyl chloride (by treatment with thionyl chloride) via a Arndt–Eistert reaction with diazomethane then by treatment with potassium phthalimide and potassium thiocyanate.[1] WP

Brand names

Pilocarpine is available under several brand names such as: Diocarpine (Dioptic), Isopto Carpine (Alcon), Miocarpine (CIBA Vision), Ocusert Pilo-20 and -40 (Alza), Pilopine HS (Alcon), Salagen (MGI Pharma), Scheinpharm Pilocarpine (Schein Pharmaceutical), Timpilo (Merck Frosst), and Vuity (AbbVie). WP

Chemistry

Formula

C11H16N2O2 PC

CAS number

92-13-7 PC

Molar mass (g/mol)

208.26 PC

IUPAC name (computed by PubChem)

(3S,4R)-3-ethyl-4-[(3-methylimidazol-4-yl)methyl]oxolan-2-one PC

SMILES

CC[C@H]1[C@H](COC1=O)CC2=CN=CN2C PC

InChIKey

QCHFTSOMWOSFHM-WPRPVWTQSA-N PC

PubChem CID

5910

IUPAC name

(3S,4R)-3-Ethyl-4-((1-methyl-1H-imidazol-5-yl)methyl)dihydrofuran-2(3H)-one WP

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Vardanyan RS, Hruby VJ. Synthesis of Essential Drugs. 2006. doi:10.1016/B978-044452166-8/50013-3
2. Other Pilocarpine
3. Other Tarascon Pocket Pharmacopoeia 2019 Deluxe Lab-Coat Edition. 2018
4. Other World Health Organization. WHO Model Formulary 2008. 2009
5. Other Glaucoma and ocular hypertension. NICE guideline 81. November 2017
6. Journal / agency Lusthaus J, Goldberg I. Current management of glaucoma. The Medical Journal of Australia. March 2019. doi:10.5694/mja2.50020 · PMID 30767238
7. Other Hamilton R. Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. 2015
8. Other Pilocarpine ophthalmic Use During Pregnancy
9. Other British national formulary: BNF 69. 2015
10. Other Sneader W. Drug Discovery: A History. 2005
11. Journal / agency Rosin A. Pilocarpine. A miotic of choice in the treatment of glaucoma has passed 110 years of use. Oftalmologia. 1991. PMID 1811739
12. Journal / agency Holmstedt B, Wassén SH, Schultes RE. Jaborandi: an interdisciplinary appraisal. Journal of Ethnopharmacology. January 1979. doi:10.1016/0378-8741(79)90014-x · PMID 397371
13. Other World Health Organization. World Health Organization model list of essential medicines: 21st list 2019. 2019
14. Journal / agency Pilocarpine
15. Journal / agency Yang WF, Liao GQ, Hakim SG, Ouyang DQ, Ringash J, Su YX. Is Pilocarpine Effective in Preventing Radiation-Induced Xerostomia? A Systematic Review and Meta-analysis. International Journal of Radiation Oncology, Biology, Physics. March 2016. doi:10.1016/j.ijrobp.2015.11.012 · PMID 26867879
16. Other Kanski JJ, Bowling B. Kanski's Clinical Ophthalmology E-Book: A Systematic Approach. 2015-03-24
17. Journal / agency Jaanus SD, Pagano VT, Bartlett JD. Clinical Ocular Pharmacology. 1989. doi:10.1016/B978-0-7506-9322-6.50011-8
18. Other Mannis MJ, Holland EJ. Cornea E-Book. September 2016
19. Other Parker J. Descemet Membrane Endothelial Keratoplasty (DMEK): A Review. 2017
20. Other Ahmed E. Comprehensive Manual of Ophthalmology. 2010
21. Journal / agency Zhang L, Weizer JS, Musch DC. Perioperative medications for preventing temporarily increased intraocular pressure after laser trabeculoplasty. The Cochrane Database of Systematic Reviews. February 2017. doi:10.1002/14651858.CD010746.pub2 · PMID 28231380 · PMC5477062
22. Journal / agency Grzybowski A, Ruamviboonsuk V. Pharmacological Treatment in Presbyopia. Journal of Clinical Medicine. March 2022. doi:10.3390/jcm11051385 · PMID 35268476 · PMC8910925
23. Journal / agency Vuity- pilocarpine hydrochloride solution/ drops
24. Other Prasad RK. Chemistry and Synthesis of Medicinal Agents: (Expanding Knowledge of Drug Chemistry). 2017-07-11
25. Journal / agency Teekhasaenee C. Glaucoma. 2015. doi:10.1016/B978-0-7020-5193-7.00073-X
26. Journal / agency Károly N. Immunohistochemical investigations of the neuronal changes induced by chronic recurrent seizures in a pilocarpine rodent model of temporal lobe epilepsy. 2018. doi:10.14232/phd.9734
27. Journal / agency Morimoto K, Fahnestock M, Racine RJ. Kindling and status epilepticus models of epilepsy: rewiring the brain. Progress in Neurobiology. May 2004. doi:10.1016/j.pneurobio.2004.03.009 · PMID 15193778
28. Journal / agency De Abreu IN, Sawaya AC, Eberlin MN, Mazzafera P. Production of Pilocarpine in Callus of Jaborandi (Pilocarpus microphyllus Stapf). In Vitro Cellular & Developmental Biology - Plant. November–December 2005. doi:10.1079/IVP2005711
29. Journal / agency Avancini G, Abreu IN, Saldaña MD, Mohamed RS, Mazzafera P. Induction of pilocarpine formation in jaborandi leaves by salicylic acid and methyljasmonate. Phytochemistry. May 2003. doi:10.1016/S0031-9422(03)00102-X · PMID 12711138
30. Journal / agency Sawaya AC, Abreu IN, Andreazza NL, Eberlin MN, Mazzafera P. HPLC-ESI-MS/MS of imidazole alkaloids in Pilocarpus microphyllus. Molecules. July 2008. doi:10.3390/molecules13071518 · PMID 18719522 · PMC6245396
31. Journal / agency Schwab L. Eye Care in Developing Nations. 2007. doi:10.1201/b15129-14

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.