Pilocarpine
Encyclopedia
Pilocarpine is a parasympathomimetic alkaloid
obtained from the leaves of tropical American shrubs from the genus
Pilocarpus
. It is a non-selective muscarinic receptor agonist
in the parasympathetic nervous system
, which acts therapeutically at the muscarinic acetylcholine receptor M3
due to its topical application, e.g., in glaucoma
and xerostomia
.
and acute angle-closure glaucoma for over 100 years. It acts on a subtype of muscarinic receptor (M3) found on the iris sphincter muscle
, causing the muscle to contract and engage in 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
.
Pilocarpine is often used as an antidote for scopolamine
, atropine
, and hyoscyamine
poisoning.
In ophthalmology pilocarpine is also used to reduce the possibility of glare at night from lights if the patient underwent implantation of phakic intraocular lens
es; the use of pilocarpine would reduce the size of the pupils, relieving these symptoms. The most common concentration for this use is pilocarpine 1%, the weakest concentration.
Pilocarpine is also used to treat dry mouth (xerostomia
) which can occur, for example, as a side effect of radiation therapy
for head and neck cancers. Pilocarpine stimulates the secretion of large amounts of saliva
and sweat
.
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
(CF).
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.
.
, increased bronchial mucus
secretion, bradycardia
, vasodilation
, brow ache
(when used as eye drops) and diarrhea
. It can also result in miosis
when used chronically as an eye drop. Systemic injection of pilocarpine can compromise the blood-brain barrier allowing the pilocarpine to gain access to the brain. This can lead to chronic epilepsy.
Epilepsy induced by pilocarpine has been used to develop animal models in rodents in order to study human epilepsy.
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
obtained from the leaves of tropical American shrubs from the genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
Pilocarpus
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...
. It is a non-selective muscarinic receptor agonist
Muscarinic receptor agonist
A muscarinic receptor agonist is an agent that enhances the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, labelled M1-M5, allowing for further differentiation.- M1 :...
in the parasympathetic nervous system
Parasympathetic nervous system
The parasympathetic nervous system is one of the two main divisions of the autonomic nervous system . The ANS is responsible for regulation of internal organs and glands, which occurs unconsciously...
, which acts therapeutically at the muscarinic acetylcholine receptor M3
Muscarinic acetylcholine receptor M3
The muscarinic acetylcholine receptor M3, also known as the cholinergic receptor, muscarinic 3, is a muscarinic acetylcholine receptor. It is encoded by the human gene CHRM3....
due to its topical application, e.g., in glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
and xerostomia
Xerostomia
Xerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...
.
Clinical
Pilocarpine has been used in the treatment of chronic open-angle glaucomaGlaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
and acute angle-closure glaucoma for over 100 years. It acts on a subtype of muscarinic receptor (M3) found on the iris sphincter muscle
Iris sphincter muscle
The iris sphincter muscle is a muscle in the part of the eye called the iris...
, causing the muscle to contract and engage in miosis
Miosis
Miosis is the constriction of the pupil of the eye to two millimeters or less...
. Pilocarpine also acts on the ciliary muscle
Ciliary muscle
The ciliary muscle is a ring of striated smooth muscle in the eye's middle layer that controls accommodation for viewing objects at varying distances and regulates the flow of aqueous humour into Schlemm's canal. It changes the shape of the lens within the eye not the size of the pupil which is...
and causes it to contract. When the ciliary muscle contracts, it opens the trabecular meshwork
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 tissue is spongy and lined by trabeculocytes; it allows fluid to drain into a set of...
through increased tension on the scleral spur. This action facilitates the rate that aqueous humor leaves the eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
to decrease intraocular pressure
Intraocular pressure
Intraocular pressure 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 from glaucoma...
.
Pilocarpine is often used as an antidote for scopolamine
Scopolamine
Scopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects. It is among the secondary metabolites of plants from Solanaceae family of plants, such as henbane, jimson weed and Angel's Trumpets , and corkwood...
, atropine
Atropine
Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...
, and hyoscyamine
Hyoscyamine
Hyoscyamine is a tropane alkaloid. It is a secondary metabolite found in certain plants of the Solanaceae family, including henbane , mandrake , jimsonweed , tomato and deadly nightshade...
poisoning.
In ophthalmology pilocarpine is also used to reduce the possibility of glare at night from lights if the patient underwent implantation of phakic intraocular lens
Intraocular lens
An intraocular lens is an implanted lens in the eye, usually replacing the existing crystalline lens because it has been clouded over by a cataract, or as a form of refractive surgery to change the eye's optical power. It usually consists of a small plastic lens with plastic side struts, called...
es; the use of pilocarpine would reduce the size of the pupils, relieving these symptoms. The most common concentration for this use is pilocarpine 1%, the weakest concentration.
Pilocarpine is also used to treat dry mouth (xerostomia
Xerostomia
Xerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...
) which can occur, for example, as a side effect of radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
for head and neck cancers. Pilocarpine stimulates the secretion of large amounts of saliva
Saliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...
and sweat
SWEAT
SWEAT is an OLN/TSN show hosted by Julie Zwillich that aired in 2003-2004.Each of the 13 half-hour episodes of SWEAT features a different outdoor sport: kayaking, mountain biking, ice hockey, beach volleyball, soccer, windsurfing, rowing, Ultimate, triathlon, wakeboarding, snowboarding, telemark...
.
Pilocarpine is used to stimulate sweat glands in a sweat test
Sweat test
The sweat test measures the concentration of chloride that is excreted in sweat. It is used to screen for cystic fibrosis .-Background:Cystic fibrosis is caused by defects in a protein found in many tissues, including the airways and the sweat glands. As a result, these tissues do not work properly...
to measure the concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...
of chloride
Chloride
The chloride ion is formed when the element chlorine, a halogen, picks up one electron to form an anion Cl−. The salts of hydrochloric acid HCl contain chloride ions and can also be called chlorides. The chloride ion, and its salts such as sodium chloride, are very soluble in water...
and sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
that is excreted in sweat. It is used to diagnose cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
(CF).
Preparation
The drug and powdered leaf of pilocarpin microfelixis are subjected to extracted forotoal alkaloid with ethanol acidified with HCl with solvents removed under reduced pressure and resultant aqueous residue is neutralized with ammonia and kept aside till all the resin is settled down completely. It is filtered and concentrated by sugar solution to a small volume, made alkaloid with ammonia, and finally extracted with chloroform. The solvent is removed under reduced pressure.Scientific
Pilocarpine is used to induce chronic epilepsyEpilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
in rodents, commonly rats
RATS
RATS may refer to:* RATS , Regression Analysis of Time Series, a statistical package* Rough Auditing Tool for Security, a computer program...
, 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
Saliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...
, for instance, to obtain information about IgA
IGA
Iga or IGA may stand for:-Given name:* a female given name of Polish origin. The name originates from the female given name Jadwiga and stands for gia,or gina in the USA....
antibodies.
Veterinary
Pilocarpine is given in moderate doses (about 2 mg) to induce emesis in cats who have ingested foreign plants, foods, or drugs. One feline trial determined it was effective, even though the usual choice of emetic is xylazineXylazine
Xylazine is a drug that is used for sedation, anesthesia, muscle relaxation, and analgesia in animals such as horses, cattle and other non-human mammals. An analogue of clonidine, it is an agonist at the α2 class of adrenergic receptor....
.
Trade names
Pilocarpine is available under several trade 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), and Timpilo (Merck Frosst).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 sweating, excessive salivation, bronchospasmBronchospasm
Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release of substances from mast cells or basophils under the influence of anaphylatoxins...
, increased bronchial mucus
Mucus
In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...
secretion, bradycardia
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
, vasodilation
Vasodilation
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
, brow ache
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
(when used as eye drops) and diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
. It can also result in miosis
Miosis
Miosis is the constriction of the pupil of the eye to two millimeters or less...
when used chronically as an eye drop. Systemic injection of pilocarpine can compromise the blood-brain barrier allowing the pilocarpine to gain access to the brain. This can lead to chronic epilepsy.
Epilepsy induced by pilocarpine has been used to develop animal models in rodents in order to study human epilepsy.
Further reading
- The Italian Journal of Neurological Sciences Volume 16, Numbers 1-2, 33-37, DOI: 10.1007/BF02229072
- Pathophysiology of Status Epilepticus Induced by Pilocarpine, central nervous system agents in medical chemistry, 2007, vol. 7, no. 1