Pilocarpine, sold under the brand name Pilopine HS among others, is a

lactone Lactones are cyclic carboxylic esters. They are derived from the corresponding hydroxycarboxylic acids by esterification. They can be saturated or unsaturated. Lactones are formed by lactonization, the intramolecular esterification of the corresp ...

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

originally extracted from plants of the

Pilocarpus ''Pilocarpus'' is a genus of about 13 species of plants belonging to the family Rutaceae, native to the Neotropics of South America. Various species are important pharmacologically as a source of the parasympathomimetic alkaloid Alkaloids ...

genus. It is used as a medication to reduce pressure inside the eye and treat dry mouth. As an

eye drop Eye drops or eyedrops are liquid drops applied directly to the surface of the eye usually in small amounts such as a single drop or a few drops. Eye drops usually contain saline to match the salinity of the eye. Drops containing only saline ...

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 syndrome Sjögren is a Swedish surname. Notable people with the surname include: * Anders Johan Sjögren (1794–1855), Finnish linguist, historian, ethnographer and explorer * Ann Mari Sjögren, Swedish fantasy artist and illustrator * Christer Sjögren, ...

radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

. Common side effects of the eye drops include irritation of the eye, increased tearing, headache, and blurry vision. Other side effects include

allergic reactions Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, alle ...

and

retinal detachment Retinal detachment is a condition where the retina pulls away from the tissue underneath it. It may start in a small area, but without quick treatment, it can spread across the entire retina, leading to serious vision loss and possibly blindness. ...

. Use is generally not recommended during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

. Pilocarpine is in the miotics family of medication. It works by activating cholinergic receptors of the muscarinic type which cause the

trabecular meshwork The trabecular meshwork is an area of tissue in the eye located around the base of the cornea, near the ciliary body, and is responsible for draining the aqueous humor from the eye via the anterior chamber (the chamber on the front of the ...

to open and the aqueous humor to drain from the eye. 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 The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. It was originally made from the South American plant ''

''.

Medical uses

Pilocarpine stimulates the secretion of large amounts of

saliva Saliva (commonly referred as spit or drool) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which ...

and

sweat Perspiration, also known as sweat, is the fluid secreted by sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and Apocrine sweat gland, apocrine glands. The eccrine sweat glands are distribu ...

. It is used to prevent or treat dry mouth, particularly in

, but also as a side effect of

for

head and neck cancer Head and neck cancer is a general term encompassing multiple cancers that can develop in the head and neck region. These include cancers of the mouth, tongue, gums and lips (oral cancer), voice box ( laryngeal), throat ( nasopharyngeal, orophary ...

. It may be used to help differentiate

Adie syndrome Adie syndrome, also known as Holmes–Adie syndrome, is a neurological disorder characterized by a tonically dilated pupil that reacts slowly to light but shows a more definite response to accommodation (i.e., light-near dissociation). It is ...

from other causes of unequal pupil size. It may be used to treat a form of dry eye called ''aqueous deficient dry eye (ADDE)''

Surgery

Pilocarpine is sometimes used immediately before certain types of corneal grafts and

cataract surgery Cataract surgery, also called lens replacement surgery, is the removal of the natural lens (anatomy), lens of the human eye, eye that has developed a cataract, an opaque or cloudy area. The eye's natural lens is usually replaced with an artific ...

. 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.

Presbyopia

In 2021, the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) approved pilocarpine hydrochloride as an

treatment for

presbyopia Presbyopia is a physiological insufficiency of optical Accommodation (vertebrate eye), accommodation associated with the aging of the human eye, eye; it results in progressively worsening ability to focus clearly on close objects. Also known as ...

, age-related difficulty with near-in vision. It works by causing the pupils to constrict, increasing

depth of field The depth of field (DOF) is the distance between the nearest and the farthest objects that are in acceptably sharp focus (optics), focus in an image captured with a camera. See also the closely related depth of focus. Factors affecting depth ...

, similar to the effect of pinhole glasses.

Other

Pilocarpine is used to stimulate sweat glands in a sweat test to measure the

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...

chloride The term chloride refers to a compound or molecule that contains either a chlorine anion (), which is a negatively charged chlorine atom, or a non-charged chlorine atom covalently bonded to the rest of the molecule by a single bond (). The pr ...

and

sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...

that is excreted in sweat. It is used to diagnose

cystic fibrosis Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...

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. Pilocarpine has been known to cause excessive salivation, sweating, bronchial

mucus Mucus (, ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both Serous fluid, serous and muc ...

secretion,

bronchospasm Bronchospasm or a bronchial spasm is a sudden bronchoconstriction, constriction of the muscles in the walls of the bronchioles. It is caused by the release (degranulation) of substances from mast cells or basophils under the influence of anaphylat ...

bradycardia Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due ...

vasodilation Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wa ...

, and

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

. Eye drops can result in brow ache and chronic use in

miosis Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...

. It can also cause temporary blurred vision or darkness of vision, temporary shortsightedness, hyphema and retinal detachment.

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 The iris sphincter muscle (pupillary sphincter, pupillary constrictor, circular muscle of iris, circular fibers) is a muscle in the part of the eye called the iris. It encircles the pupil of the iris, appropriate to its function as a constricto ...

, causing the muscle to contract - resulting in pupil constriction (

miosis Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...

). Pilocarpine also acts on the

ciliary muscle The ciliary muscle is an intrinsic muscle of the eye formed as a ring of smooth muscleSchachar, Ronald A. (2012). "Anatomy and Physiology." (Chapter 4) . in the eye's middle layer, the uvea ( vascular layer). It controls accommodation for vie ...

and causes it to contract. When the ciliary muscle contracts, it opens the

through increased tension on the scleral spur. This action facilitates the rate that aqueous humor leaves the

eye An eye is a sensory organ that allows an organism to perceive visual information. It detects light and converts it into electro-chemical impulses in neurons (neurones). It is part of an organism's visual system. In higher organisms, the ey ...

to decrease

intraocular pressure Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Most tonometers are calibrated t ...

. Paradoxically, when pilocarpine induces this ciliary muscle contraction (known as an accommodative spasm) it causes the eye's

lens A lens is a transmissive optical device that focuses or disperses a light beam by means of refraction. A simple lens consists of a single piece of transparent material, while a compound lens consists of several simple lenses (''elements'') ...

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

Society and culture

Preparation

Plants in the genus ''

'' 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. Pilocarpine is extracted from the leaves of Pilocarpus microphyllus in a multi-step process : the sample is moistened with dilute

sodium hydroxide Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula . It is a white solid ionic compound consisting of sodium cations and hydroxide anions . Sodium hydroxide is a highly corrosive base (chemistry), ...

to transform the alkaloid into its free-base form then extracted using

chloroform Chloroform, or trichloromethane (often abbreviated as TCM), is an organochloride with the formula and a common solvent. It is a volatile, colorless, sweet-smelling, dense liquid produced on a large scale as a precursor to refrigerants and po ...

or a suitable organic solvant. Pilocarpine can then be further purified by re-extracting the resulting solution with aqueous

sulfuric acid Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid (English in the Commonwealth of Nations, Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen, ...

then readjusting the pH to basic using

ammonia Ammonia is an inorganic chemical compound of nitrogen and hydrogen with the chemical formula, formula . A Binary compounds of hydrogen, stable binary hydride and the simplest pnictogen hydride, ammonia is a colourless gas with a distinctive pu ...

and a final extraction by chloroform. It can also be synthesized from 2-ethyl-3-carboxy-2-butyrolactone in a 8 steps process from the acyl chloride (by treatment with

thionyl chloride Thionyl chloride is an inorganic compound with the chemical formula . It is a moderately Volatility (chemistry), volatile, colourless liquid with an unpleasant acrid odour. Thionyl chloride is primarily used as a Halogenation, chlorinating reagen ...

) via a Arndt–Eistert reaction with

diazomethane Diazomethane is an organic chemical compound with the formula CH2N2, discovered by German chemist Hans von Pechmann in 1894. It is the simplest diazo compound. In the pure form at room temperature, it is an extremely sensitive explosive yellow ga ...

then by treatment with potassium phthalimide and

potassium thiocyanate Potassium thiocyanate is the chemical compound with the molecular formula KSCN. It is an important salt of the thiocyanate anion, one of the pseudohalides. The compound has a low melting point relative to most other inorganic salts. Uses Ch ...

Brand names

Pilocarpine is available under several brand names such as: Diocarpine (Dioptic), Isopto Carpine (

Alcon Alcon Inc. () is a Swiss-American pharmaceutical and medical device company specializing in eye care products. It has a paper headquarters in Geneva, Switzerland but its operational headquarters are in Fort Worth, Texas, United States, where it ...

), 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).

Research

Pilocarpine is used to induce chronic

epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...

rodent Rodents (from Latin , 'to gnaw') are mammals of the Order (biology), order Rodentia ( ), which are characterized by a single pair of continuously growing incisors in each of the upper and Mandible, lower jaws. About 40% of all mammal specie ...

s, commonly

rat Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include '' Neotoma'' (pack rats), '' Bandicota'' (bandicoo ...

s, 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

, for instance, to obtain information about IgA antibodies.

References

External links

{{Authority control Alkaloids found in Rutaceae Drugs developed by Novartis Drugs developed by Pfizer Gamma-lactones Imidazoles M1 receptor agonists M2 receptor agonists M3 receptor agonists M4 receptor agonists M5 receptor agonists Ophthalmology drugs Tetrahydrofurans Wikipedia medicine articles ready to translate World Health Organization essential medicines