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Pilocarpine
Clinical data
Trade namesIsopto Carpine, Salagen, others
AHFS/Drugs.comMonograph
MedlinePlusa608039
License data
Pregnancy
category
  • AU: B3
Routes of
administration		Ophthalmic, by mouth
Drug class
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life0.76 hours (5 mg), 1.35 hours (10 mg)[3]
ExcretionUrine
Identifiers
  • (3S,4R)-3-Ethyl-4-((1-methyl-1H-imidazol-5-yl)methyl)dihydrofuran-2(3H)-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.001.936 Edit this at Wikidata
Chemical and physical data
FormulaC11H16N2O2
Molar mass208.261 g·mol−1
3D model (JSmol)
  • O=C2OC[C@H](Cc1n(cnc1)C)[C@@H]2CC
  • InChI=1S/C11H16N2O2/c1-3-10-8(6-15-11(10)14)4-9-5-12-7-13(9)2/h5,7-8,10H,3-4,6H2,1-2H3/t8-,10-/m0/s1 checkY
  • Key:QCHFTSOMWOSFHM-WPRPVWTQSA-N checkY
  (verify)

Pilocarpine is a lactone alkaloid originally extracted from plants of the Pilocarpus genus.[4] It is used as a medication to reduce pressure inside the eye and treat dry mouth.[1][5] 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.[1][6][7] However, due to its side effects, it is no longer typically used for long-term management.[8] Onset of effects with the drops is typically within an hour and lasts for up to a day.[1] By mouth it is used for dry mouth as a result of Sjögren syndrome or radiation therapy.[9]

Common side effects of the eye drops include irritation of the eye, increased tearing, headache, and blurry vision.[1] Other side effects include allergic reactions and retinal detachment.[1] Use is generally not recommended during pregnancy.[10] Pilocarpine is in the miotics family of medication.[11] 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.[1]

Pilocarpine was isolated in 1874 by Hardy and Gerrard and has been used to treat glaucoma for more than 100 years.[12][13][14] It is on the World Health Organization's List of Essential Medicines.[15] It was originally made from the South American plant Pilocarpus.[12]

Medical uses

[edit]

Pilocarpine stimulates the secretion of large amounts of saliva and sweat.[16] 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.[17]

It may be used to help differentiate Adie syndrome from other causes of unequal pupil size.[18][19]

It may be used to treat a form of dry eye called aqueous deficient dry eye (ADDE).[20]

Surgery

[edit]

Pilocarpine is sometimes used immediately before certain types of corneal grafts and cataract surgery.[21][22] 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.[dubious – discuss] The most common concentration for this use is pilocarpine 1%.[citation needed] Pilocarpine is shown to be just as effective as apraclonidine in preventing intraocular pressure spikes after laser trabeculoplasty.[23]

Presbyopia

[edit]

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.[24][2]

Other

[edit]

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.[25]

Adverse effects

[edit]

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.

Pharmacology

[edit]

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.[26]

Society and culture

[edit]

Preparation

[edit]

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.[27]

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.[28][29][30]

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) via a Arndt–Eistert reaction with diazomethane then by treatment with potassium phthalimide and potassium thiocyanate.[4]

Brand names

[edit]

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).

Research

[edit]

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.[31][32] Smaller doses may be used to induce salivation in order to collect samples of saliva, for instance, to obtain information about IgA antibodies.

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Pilocarpine

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from Grokipedia
Pilocarpine is a naturally occurring derived from the leaves of Pilocarpus jaborandi, a in the family native to . First isolated in , it functions as a muscarinic that stimulates the by mimicking the action of at muscarinic receptors. In medicine, pilocarpine is primarily administered in two forms: ophthalmic solutions and oral tablets. Ophthalmic pilocarpine reduces by constricting the and facilitating aqueous humor outflow, making it a longstanding treatment for open-angle and angle-closure , as well as . Low-dose formulations, such as 1.25% pilocarpine (branded as Vuity), have also been approved for improving near vision in by inducing temporary . Orally, pilocarpine increases salivary and secretion to relieve (dry mouth) caused by head and neck in cancer patients or associated with Sjögren's syndrome, an autoimmune disorder. Despite its efficacy, pilocarpine's use is tempered by potential side effects, including , sweating, , and cardiovascular changes due to its effects. It remains a valuable therapeutic agent in and sialagogue , with ongoing research exploring its applications in other conditions like induction and .

History

Discovery and isolation

Pilocarpine is derived from the leaves of the jaborandi shrub, a species native to the tropical regions of , particularly and . in these areas have long utilized the leaves of this plant in , employing infusions or decoctions to induce salivation and for treating conditions such as fevers, , and respiratory ailments. The active pilocarpine was first isolated in 1875 through independent efforts by French chemist E. Hardy and British chemist Alfred William Gerrard, who extracted it from jaborandi leaves using alcoholic solutions followed by precipitation and crystallization techniques. This isolation marked pilocarpine as a key alkaloid responsible for the plant's pharmacological effects, with early characterizations confirming its basic nature and properties. The of pilocarpine was elucidated in the early , primarily through degradation studies conducted by British chemist Hooper Albert Dickinson Jowett between 1901 and 1905, revealing it as a bicyclic compound featuring an ring attached to a dihydrofuranone () moiety. Its molecular formula is C₁₁H₁₆N₂O₂, with the systematic IUPAC name (3S,4R)-3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl]-2(3H)-furanone. Initial pharmacological investigations shortly after isolation demonstrated pilocarpine's properties, including stimulation of salivary and sweat glands as well as , paving the way for its adoption in early medical applications such as treatment.

Early medical applications

Pilocarpine was first introduced into medical practice in 1876 by Austrian ophthalmologist Alexander Weber, who used the isolated Pilocarpium muriaticum from the leaves of jaborandi to treat by inducing and thereby reducing . This marked the initial therapeutic application of pilocarpine in , building on its prior isolation as a natural compound. One year later, in 1877, it was adopted as a local miotic agent, supplanting the use of Calabar bean extract () due to its more reliable and potent effects on pupillary constriction. By the 1880s, pilocarpine had been formulated into ophthalmic solutions, or eye drops, which facilitated its widespread adoption as a standard treatment for open-angle glaucoma. These preparations allowed for targeted delivery to the eye, promoting contraction of the ciliary muscle and trabecular meshwork to enhance aqueous humor outflow and lower intraocular pressure. Pilocarpine quickly became a cornerstone of glaucoma management, remaining the primary miotic therapy for decades and demonstrating efficacy in controlling pressure in a majority of patients with chronic open-angle disease. In the early , pilocarpine's properties led to its expansion beyond , particularly as a sialogogue to induce salivation for diagnostic evaluation of function and in cases of hyposalivation. Initial reports of its use to stimulate dated to the late among indigenous South American populations, but clinical adoption in Western medicine grew in the subsequent decades for assessing glandular responsiveness. By , pilocarpine had earned inclusion in major pharmacopeias, such as the , affirming its established role in therapeutics. Throughout the first half of the , pilocarpine maintained prominence in treatment, with formulations refined to improve tolerability, though it required frequent administration—typically four to six times daily—to sustain therapeutic effects. This dosing regimen, combined with systemic side effects like brow ache and accommodative , often led to poor patient compliance and limited long-term adherence. Its dominance persisted until the , when the advent of once-daily analogs offered more convenient alternatives, gradually reducing pilocarpine's centrality in regimens.

Medical uses

Glaucoma treatment

Pilocarpine serves as a primary topical agent in the management of open-angle glaucoma, where it lowers intraocular pressure (IOP) by contracting the longitudinal fibers of the ciliary muscle. This contraction pulls on the scleral spur, opening the trabecular meshwork and enhancing the outflow of aqueous humor, thereby reducing IOP by approximately 20–30% in a dose-dependent manner. The standard dosing regimen for pilocarpine ophthalmic solution involves concentrations of 1–4%, administered as 1–2 drops in the affected eye(s) up to four times daily, with adjustments based on disease severity and patient response. It is frequently combined with beta-blockers like timolol to achieve additive IOP-lowering effects, as demonstrated in comparative studies where such combinations provided superior pressure control compared to monotherapy. Pilocarpine is particularly suitable for patients with mild to moderate open-angle glaucoma, offering effective IOP reduction of 3–7 mmHg in clinical settings. However, its use has declined in favor of newer agents with improved tolerability profiles, owing to frequent dosing requirements and side effects such as and accommodation spasm. Ongoing management includes regular IOP monitoring to assess treatment efficacy and progression, alongside patient education on coping with transient blurred vision due to induced accommodation.

Presbyopia treatment

In 2021, the U.S. Food and Drug Administration (FDA) approved 1.25% pilocarpine hydrochloride ophthalmic solution (Vuity) for the treatment of presbyopia in adults aged 40 years and older. This low-dose formulation targets age-related loss of near vision by inducing mild miosis, which creates a pinhole effect that increases the depth of field and enhances uncorrected near visual acuity without significantly affecting distance vision. The recommended dosing is one drop in each eye once daily, typically in the morning, with effects beginning within 15 minutes and providing improvement in near vision for up to 6 hours on day 30 of use. Clinical trials demonstrated that Vuity improves uncorrected near by at least 3 lines on the Early Treatment Study (ETDRS) in approximately 67% of patients at 3 hours post-instillation, with 40% maintaining this gain at 10 hours in some cases; however, it does not correct distance vision and offers only temporary relief. Limitations include its short duration of action, requiring daily reapplication, and caution in patients with due to potential intraocular pressure reduction, necessitating monitoring by an . Additionally, recent studies have indicated an increased risk of rhegmatogenous retinal detachment associated with topical pilocarpine for , particularly in patients with risk factors such as , lattice degeneration, or vitreous degeneration; patients should be informed of this risk and monitored accordingly. In 2023, the FDA approved a lower-concentration 0.4% pilocarpine hydrochloride ophthalmic solution (Qlosi) for treatment in adults, aiming to minimize side effects while maintaining efficacy through the same pinhole mechanism. Dosing remains one drop in each eye once daily, with showing significant near vision improvement comparable to higher doses but with reduced incidence of adverse effects such as and eye pain. Like Vuity, Qlosi provides temporary benefits and requires similar precautions for patients, as well as awareness of the potential retinal detachment risk noted above.

Xerostomia treatment

Pilocarpine hydrochloride, marketed under the brand name Salagen, received FDA approval on March 22, 1994, for the treatment of symptoms of resulting from salivary gland hypofunction caused by radiotherapy for . On February 11, 1998, the FDA expanded approval to include the treatment of dry mouth in patients with Sjögren's syndrome. These approvals were based on clinical trials demonstrating its ability to alleviate symptoms through in tablet form. The recommended dosing for is 5 mg tablets taken three times daily for post-radiation cases (with a maximum of 30 mg per day, not exceeding 10 mg per dose) and four times daily for Sjögren's syndrome (up to 20 mg per day). Pilocarpine acts as a agonist, stimulating muscarinic receptors in the salivary glands to promote . In clinical studies, this regimen has been shown to increase unstimulated salivary flow by 63% at 5 mg doses and up to 90% at 10 mg doses in patients with radiation-induced , with noticeable effects emerging within weeks of consistent use. Efficacy data from randomized controlled trials indicate that pilocarpine significantly improves xerostomia-related symptoms, including difficulty , oral discomfort, and speaking, while also reducing the risk of secondary complications such as oral infections due to enhanced salivary lubrication and properties. Response rates, defined as subjective global improvement in dry mouth symptoms, approximate 50% in treated patients compared to , with benefits observed in about 47% of participants in multicenter studies. Pilocarpine is suitable for patients with confirmed salivary gland hypofunction, such as those who have received at least 4,000 centigray of to the head and neck or have primary Sjögren's syndrome, but it is not indicated for acute or transient dry mouth episodes. Treatment duration for post- is generally assessed over 12 weeks, with potential extension up to 3 months if response is favorable; for chronic Sjögren's syndrome, long-term use may be appropriate under medical supervision.

Other uses

Pilocarpine is employed intraoperatively during to induce , typically using a 1-2% solution administered intracamerally or topically, which constricts the and helps maintain anterior chamber depth by stabilizing the capsular bag and reducing iris risk. This approach is particularly useful in cases of small pupils or , allowing better surgical access and maneuverability. In emergencies involving angle-closure , pilocarpine serves as an adjunctive agent before laser peripheral iridotomy, with a 1-2% solution instilled to constrict the and pull the iris away from the , thereby improving aqueous humor outflow temporarily. The American Academy of Ophthalmology guidelines endorse its use in such acute scenarios to lower rapidly prior to definitive laser therapy. Off-label applications include prevention of cystoid following ocular surgery, where low-dose pilocarpine may reduce inflammation-related complications, though evidence remains limited and it is not routinely recommended due to potential risks. In neonatal , pilocarpine (1-2%) is used rarely and primarily preoperatively at 2-3 times daily to constrict the and enhance visualization during goniotomy, as it is less effective for long-term control in infants. Historically, pilocarpine has been utilized for diagnostic miosis testing, such as the dilute pilocarpine test (0.125% or lower) to identify Adie's tonic pupil by assessing denervation supersensitivity, though this application is now less common with advanced imaging. For dry eye syndrome, topical or oral pilocarpine has shown limited evidence of benefit beyond specific cases like Sjögren's syndrome, with early studies indicating short-term symptom relief but poor long-term efficacy due to side effects and inconsistent tear production stimulation.

Contraindications and adverse effects

Contraindications

Pilocarpine is contraindicated in patients with known to pilocarpine or any of its components, as this may lead to severe allergic reactions. For systemic formulations, it is absolutely contraindicated in individuals with uncontrolled due to the potential for and increased bronchial secretions. Ophthalmic use requires caution in patients with due to possible minor systemic absorption. Ophthalmic administration is specifically contraindicated in acute iritis, as it may exacerbate . It should be used with caution in untreated narrow-angle at risk of pupillary block but is indicated for the initial management of acute angle-closure . Similarly, systemic pilocarpine should be avoided in acute iritis or narrow-angle , as it may induce and worsen these conditions. In patients with severe hepatic impairment (Child-Pugh class C), systemic pilocarpine is not recommended due to altered and lack of data, while moderate impairment requires dosage reduction and careful monitoring. No dosage adjustment is typically needed for renal impairment, as remain comparable to normal renal function. Pilocarpine is classified as C, meaning animal studies show adverse fetal effects, but it may be used if the potential benefit justifies the risk to the ; limited human data are available. Drug interactions warrant caution: systemic pilocarpine may potentiate effects when combined with other cholinergics such as , leading to excessive parasympathomimetic activity, and should be used carefully with beta-blockers due to risks of cardiac conduction disturbances. In pediatric patients, and of systemic pilocarpine have not been established, and it should be avoided in infants; ophthalmic use requires caution in young children with certain types due to potential paradoxical increases. For geriatric patients, increased sensitivity to cholinergic effects may necessitate lower starting doses and close monitoring, particularly for systemic administration.

Adverse effects

Pilocarpine, when administered ophthalmically, commonly causes due to its miotic effects on the and accommodation, affecting more than 5% of patients in clinical trials. and brow ache are also frequent, reported in over 5% of users, often resulting from contraction. Other common ocular effects include conjunctival hyperemia (eye redness) in greater than 5% of cases, eye , and increased lacrimation, with incidences ranging from 1-5%. Night blindness or dim vision may occur transiently, particularly in low-light conditions, as a result of . Additionally, some patients experience a transient spike in shortly after instillation, though this is less common with lower concentrations like 1.25%. Systemic administration of oral pilocarpine, such as in tablets for , leads to cholinergic side effects exceeding 20% incidence in many users. Excessive sweating is the most prevalent, occurring in up to 68% of patients at higher doses like 10 mg three times daily. affects 15%, 14%, 15%, and urinary frequency 12% of patients, with these rates dose-dependent and higher than . Other common effects include flushing (13%), dizziness (12%), and asthenia (12%), particularly in patients on 15-30 mg/day regimens. In Sjögren's syndrome patients on 20 mg/day, sweating still reaches 40%, with urinary frequency at 10% and at 9%. Serious adverse effects are rare but can include , , and due to parasympathetic overstimulation. Allergic reactions, such as or , have been reported postmarketing, though frequency is not reliably estimable. Cardiovascular effects like these are more pronounced with systemic use and may require monitoring. The incidence of adverse effects is dose-dependent; for ophthalmic use, higher concentrations like 4% increase reports of , , and accommodative changes compared to 1.25% formulations, where rates are lower (e.g., >5% vs. higher in traditional drops). Management often involves dose reduction or discontinuation, with sweating as the leading cause of withdrawal in oral (up to 12%). Long-term use may lead to tolerance development for some effects like sweating, but elderly patients require monitoring for increased cardiovascular risks, including higher incidences of urinary frequency, , and . Rare postmarketing reports for ophthalmic pilocarpine include vitreous detachment, vitreomacular traction, retinal tear, and detachment, associated with miotic agents.

Pharmacology

Mechanism of action

Pilocarpine acts as a direct at muscarinic receptors (mAChRs), mimicking the effects of endogenous to stimulate parasympathetic activity. It binds non-selectively to all five mAChR subtypes (M1 through M5), though its primary therapeutic effects are mediated via the M3 subtype, which is coupled to proteins. This activation does not involve nicotinic receptors. Upon binding, pilocarpine triggers G-protein-coupled , primarily through the Gq pathway for M3 receptors. This leads to of , hydrolysis of (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), and subsequent release of intracellular calcium from stores. The elevated calcium levels mediate downstream physiological responses, such as smooth muscle contraction and glandular , with receptor typically lasting 1-2 hours before desensitization or clearance influences the effect. In the eye, pilocarpine primarily targets M3 receptors on the , inducing contraction and pupillary constriction (), and on the , promoting contraction that enhances accommodation and tightens the to facilitate aqueous humor outflow. This mechanism reduces without significantly altering aqueous production. Systemically, it stimulates M3 receptors on salivary acinar cells to increase secretion via calcium-dependent of secretory granules; it exerts minor stimulatory effects on lacrimal and sweat glands through similar pathways.

Pharmacokinetics

Pilocarpine is rapidly absorbed following , with peak plasma concentrations achieved in approximately 0.85 to 1.25 hours after doses of 5 to 10 mg. The drug is well absorbed as a tertiary amine alkaloid, exhibiting high consistent with minimal first-pass . A high-fat slightly delays the rate of absorption (Tmax increased to 1.47 hours) but has no significant effect on the overall extent of absorption. For topical ophthalmic administration, such as in 1.25% solutions, systemic absorption is minimal, resulting in low plasma exposure with mean maximum concentrations of about 1.95 ng/mL and area under the curve of approximately 4.14 ng·h/mL after multiple doses. Following absorption, pilocarpine distributes widely throughout the body, with a steady-state of approximately 2.3 L/kg in humans based on intravenous data. It readily crosses the blood-ocular barrier, enabling its therapeutic effects in treatment, and achieves concentrations in ocular tissues sufficient for local action. is negligible, with less than 5% bound across a wide concentration range (5 to 25,000 ng/mL). Pilocarpine is metabolized primarily to inactive metabolites, including pilocarpic acid via hydrolysis by paraoxonase 1 (PON1) and 3-hydroxypilocarpine via CYP2A6-mediated 3-hydroxylation. Excretion occurs predominantly via the kidneys, with pilocarpine and its metabolites eliminated in the . The elimination is short, ranging from 0.76 hours after a 5 mg oral dose to 1.35 hours after a 10 mg dose, contributing to its rapid onset of action via muscarinic receptor stimulation. For topical ophthalmic use, the is longer at about 4 hours, reflecting slower systemic clearance at low exposure levels. In special populations, remain largely unchanged in renal impairment ( clearance 10-40 mL/min), but and exposure are prolonged in moderate hepatic impairment (up to twofold increase in area under the curve), necessitating dose adjustments.

Society and culture

Brand names and formulations

Pilocarpine is commercially available in several brand name products and formulations, tailored primarily for to treat or as ophthalmic solutions and gels for , , and . The primary oral formulation is Salagen, which consists of 5 mg pilocarpine hydrochloride tablets indicated for the treatment of associated with Sjögren's syndrome or for . Developed by MGI Pharma, Salagen has been available in generic form since the early . Ophthalmic formulations include eye drops such as Isopto Carpine (pilocarpine hydrochloride 0.25% to 4% solutions, manufactured by ), Piloptic (pilocarpine hydrochloride 1% to 6% solutions), Vuity (pilocarpine hydrochloride 1.25% solution for , manufactured by , an company), and Qlosi (pilocarpine hydrochloride 0.4% solution for , manufactured by Orasis Pharmaceuticals). Other delivery forms encompass ocular inserts like Ocusert (pilocarpine-releasing system, now discontinued but historically significant for sustained release in treatment) and gels such as Pilopine HS (pilocarpine 4% gel). Generic versions of pilocarpine are widely available since the 2000s, with ophthalmic solutions in concentrations of 0.25% to 6% and oral tablets in 5 mg and 7.5 mg strengths, though specific concentrations and formulations may vary by country. Pilocarpine is classified as a prescription-only (Rx-only) throughout the world, including in the United States, (Schedule S4), and the (POM). It is not designated as a under the U.S. or equivalent international schedules, reflecting its low potential for abuse. In the United States, the (FDA) first approved pilocarpine for ophthalmic use as a pre-1938 drug, long established for treating and reducing elevated . The oral formulation, Salagen (pilocarpine tablets), received FDA approval in 1994 for managing associated with or Sjögren's syndrome. Subsequent approvals include Vuity (pilocarpine ophthalmic solution 1.25%) in 2021 and Qlosi (pilocarpine ophthalmic solution 0.4%, commercially available since early 2025) in 2023, both for treating in adults. Pilocarpine has been included on the World Health Organization's Model List of Essential Medicines since 1977, specifically under ophthalmological preparations for glaucoma management, underscoring its global importance for accessible eye care. Generic versions of pilocarpine are widely available in the United States and the European Union, facilitating broader access for approved indications. In the U.S., generic oral pilocarpine typically costs $10–20 per month for a standard supply, while branded presbyopia drops like Vuity are priced higher at approximately $80–85 per vial.

Research

Emerging applications

Pilocarpine is under investigation for the treatment of opioid-induced xerostomia in cancer pain patients, building on its established role in managing radiation-induced dry mouth. A double-blind, randomized controlled trial demonstrated that oral pilocarpine (5 mg) significantly increased salivary flow from 0.15 mL/min post-opioid induction to 0.66 mL/min, compared to no change with placebo, indicating potential relief though in a model using healthy volunteers with tramadol. A pilot study in advanced cancer patients receiving opioids reported pilocarpine as safe and effective for reducing xerostomia symptoms with rapid onset in most cases, supporting further exploration despite the small sample size. Although a planned phase III trial for this indication was terminated due to poor accrual without yielding results, these findings suggest modest efficacy warrants additional phase II/III studies in oncology settings. In glaucoma management, pilocarpine is being explored for neuroprotective effects, particularly in combination with antioxidants to preserve retinal ganglion cells (RGCs). Preclinical evaluations of pilocarpine-loaded, antioxidant-functionalized thermogels in models showed sustained reduction alongside protection against oxidative stress-induced RGC damage, highlighting a dual therapeutic approach. studies have shown that pilocarpine, as a muscarinic receptor , inhibits glutamate-induced in rat RGCs via M1 receptor activation, suggesting potential as an adjunct neuroprotectant beyond its miotic action. Preclinical studies have explored combinations of pilocarpine with antioxidants to address both and cellular degeneration in . For dry eye disease, low-dose oral and topical pilocarpine formulations are in clinical trials targeting evaporative subtypes, with studies from 2023 onward evaluating symptom relief and safety. A phase 2 multicenter trial (NCT05119920) has assessed pilocarpine ophthalmic topical cream for the treatment of dry eye disease. Single-dose oral pilocarpine (5 mg) relieved both ocular and oral dryness in over 85% of patients in a 2023 prospective study, supporting its utility in evaporative dry eye linked to meibomian gland dysfunction. Additional 2023-2025 trials, including those for Sjögren's-associated dry eye, report favorable structural changes in tear film stability with low-dose regimens (e.g., 20 mg daily oral), though long-term data remain pending. Pediatric applications of pilocarpine are expanding for congenital , with recent emphasizing cautious use to avoid paradoxical elevation. Package insert updates and clinical guidelines from 2023-2025 highlight pilocarpine's role in for angle-closure prevention in children, but warn of risks in primary congenital cases due to potential pupillary block. A 2023 of pharmacological treatments in childhood included pilocarpine (1%) as an adjunct, noting acceptable profiles in select postoperative scenarios based on observational from over 70 eyes, though randomized trials are limited. Formulation innovations focus on long-acting pilocarpine and systems to minimize dosing frequency and enhance . Poly(DL-lactic-co-glycolic acid) loaded with pilocarpine achieved controlled release over 24 hours in ocular models, reducing miotic side effects while maintaining control. Chitosan-carbopol formulations demonstrated gradual pilocarpine release superior to conventional drops or gels, with in studies showing up to 4-hour sustained delivery for therapy. These advancements, including thermogels and , aim to improve patient adherence by extending duration from multiple daily doses to once or twice daily.

Experimental models

Pilocarpine serves as a key agent in preclinical to induce animal models of neurological and physiological disorders, primarily through its action as a muscarinic . In studies, systemic administration of pilocarpine at doses of 300-400 mg/kg in triggers cholinergic overstimulation, leading to (SE) and subsequent development of a mesial temporal lobe (mTLE) model characterized by spontaneous recurrent seizures and hippocampal pathology. This model recapitulates key features of human temporal lobe , including neurodegeneration and cognitive comorbidities, allowing researchers to investigate epileptogenesis mechanisms and screen antiepileptic compounds. In glaucoma research, intracameral injection of pilocarpine in rabbits and mice is employed to examine acute alterations in (IOP) dynamics, often in established models to assess miotic effects on aqueous humor outflow. These experiments help elucidate the drug's role in modulation and pupil constriction, providing insights into outflow pathway physiology without directly inducing elevation but simulating therapeutic responses to IOP fluctuations. For salivary gland investigations, pilocarpine is utilized to stimulate mechanisms in acinar cells isolated from glands, revealing pathways such as calcium mobilization and protein synthesis regulation. These studies demonstrate how pilocarpine activates muscarinic receptors to enhance release and fluid , aiding understanding of glandular function in conditions like . Despite its utility, the pilocarpine model has limitations, including high-dose toxicity that results in significant animal mortality (up to 50% in untreated SE induction) and peripheral cholinergic side effects like salivation and convulsions. Ethical concerns arise from the distress caused by prolonged SE, prompting adherence to guidelines for minimizing animal suffering in such cholinergic induction protocols. Recent advancements in the have refined these models through genetic modifications, such as using muscarinic receptor mice or optogenetic tools to target specific neuronal circuits, improving specificity for screening while reducing off-target effects. Protocols incorporating pretreatment with have also enhanced survival rates to over 80%, enabling more reliable assessment of epileptogenic processes.

References

  1. https://pubchem.ncbi.nlm.nih.gov/compound/Pilocarpine
  2. https://pmc.ncbi.nlm.nih.gov/articles/PMC3901206/
  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC11795007/
  4. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8c546251-60ab-499c-a61c-1f678ed548eb
  5. https://www.mayoclinic.org/drugs-supplements/pilocarpine-ophthalmic-route/description/drg-20065516
  6. https://medlineplus.gov/druginfo/meds/a608039.html
  7. https://www.mayoclinic.org/drugs-supplements/pilocarpine-oral-route/description/drg-20065496
  8. https://pubmed.ncbi.nlm.nih.gov/7705213/
  9. https://pmc.ncbi.nlm.nih.gov/articles/PMC9230966/
  10. https://tropical.theferns.info/viewtropical.php?id=Pilocarpus+jaborandi
  11. https://www.henriettes-herb.com/eclectic/kings/pilocarpus.html
  12. https://pmc.ncbi.nlm.nih.gov/articles/PMC546337/
  13. https://www.scribd.com/document/510911611/1604-4178-2
  14. https://pubmed.ncbi.nlm.nih.gov/397371/
  15. https://pubmed.ncbi.nlm.nih.gov/794570/
  16. https://pubmed.ncbi.nlm.nih.gov/18175440/
  17. https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.733080/full
  18. https://www.ophthalmologytimes.com/view/tracing-history-glaucoma-drugs
  19. https://glaucomatoday.com/articles/2022-sept-oct/the-return-of-pilocarpine
  20. https://pmc.ncbi.nlm.nih.gov/articles/PMC7794042/
  21. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/200890s001lbl.pdf
  22. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=d2ded29a-448d-4c4a-9307-403836a67da4
  23. https://pubmed.ncbi.nlm.nih.gov/12204713/
  24. https://pmc.ncbi.nlm.nih.gov/articles/PMC8927535/
  25. https://webeye.ophth.uiowa.edu/eyeforum/books/glaucoma_guide/chapter7.html
  26. https://medlineplus.gov/druginfo/meds/a682874.html
  27. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2021/214028Orig1s000ltr.pdf
  28. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/214028Orig1s000MedR.pdf
  29. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214028s000lbl.pdf
  30. https://www.ajo.com/article/S0002-9394(24)00517-8/fulltext
  31. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/217836Orig1s000Approv.pdf
  32. https://pubmed.ncbi.nlm.nih.gov/38216351/
  33. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=45990
  34. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=62091
  35. https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/020237s012lbl.pdf
  36. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/414409
  37. https://www.mdpi.com/1424-8247/15/6/762
  38. https://www.jfophth.com/preservative-free-intracameral-pilocarpine-for-intraoperative-miosis/
  39. https://www.sciencedirect.com/science/article/abs/pii/S0886335016000183
  40. https://ascrs.org/-/media/files/clinical-committee-reports/medical-and-surgical-management-of-the-small-pupil.pdf
  41. https://www.aao.org/education/munnerlyn-laser-surgery-center/angleclosure-glaucoma-19
  42. https://www.reviewofoptometry.com/article/angleclosure-glaucoma-are-you-ready
  43. https://jamanetwork.com/journals/jamaophthalmology/fullarticle/265670
  44. https://www.ncbi.nlm.nih.gov/books/NBK574553/
  45. https://eyewiki.org/Primary_Congenital_Glaucoma
  46. https://www.nature.com/articles/s41598-021-89148-w
  47. https://clspectrum.com/issues/2000/january/the-history-of-dry-eye-diagnosis-and-management/
  48. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/214028Orig1s003lbl.pdf
  49. https://www.nlm.nih.gov/medlineplus/druginfo/meds/a608039.html
  50. https://pmc.ncbi.nlm.nih.gov/articles/PMC5635516/
  51. https://www.ncbi.nlm.nih.gov/books/NBK553130/
  52. https://pmc.ncbi.nlm.nih.gov/articles/PMC12574428/
  53. https://pmc.ncbi.nlm.nih.gov/articles/PMC6493181/
  54. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/pilocarpine
  55. https://pubmed.ncbi.nlm.nih.gov/1409379/
  56. https://go.drugbank.com/drugs/DB01085
  57. https://pubmed.ncbi.nlm.nih.gov/21521796/
  58. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=62eda83d-d043-4c7e-8fcf-75d05efbf35b
  59. https://www.drugs.com/availability/generic-salagen.html
  60. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/200890s000OtherR.pdf
  61. https://www.blinkhealth.com/piloptic-2
  62. https://www.orasis-pharma.com/orasis-pharmaceuticals-announces-fda-approval-of-qlosi-pilocarpine-hydrochloride-ophthalmic-solution-0-4-for-the-treatment-of-presbyopia/
  63. https://www.drugs.com/sfx/ocusert-side-effects.html
  64. https://www.rxlist.com/pilopine-hs-drug.htm
  65. https://www.drugs.com/availability/generic-isopto-carpine.html
  66. https://www.drugs.com/cons/pilocarpine-oral.html
  67. https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf
  68. https://www.accessdata.fda.gov/drugsatfda_docs/pediatric/200890_pilocarpine_clinpharm_PREA.pdf
  69. https://www.medicinenet.com/pilocarpine/article.htm
  70. https://news.abbvie.com/2021-10-29-U-S-Food-and-Drug-Administration-Approves-VUITY-TM-pilocarpine-HCI-ophthalmic-solution-1-25-%2C-the-First-and-Only-Eye-Drop-to-Treat-Presbyopia-Age-Related-Blurry-Near-Vision
  71. https://www.ophthalmologytimes.com/view/the-emerging-era-of-presbyopia-correcting-eye-drops-what-s-next-
  72. https://list.essentialmeds.org/medicines/236
  73. https://www.ema.europa.eu/en/documents/psusa/pilocarpine-non-ophthalmic-formulations-list-nationally-authorised-medicinal-products-psusa00002409202207_en.pdf
  74. https://www.goodrx.com/salagen
  75. https://www.wellrx.com/prescriptions/vuity/60484
  76. https://pubmed.ncbi.nlm.nih.gov/15111631/
  77. https://pubmed.ncbi.nlm.nih.gov/11219883/
  78. https://clinicaltrials.gov/study/NCT00003686
  79. https://www.nature.com/articles/srep42344
  80. https://pmc.ncbi.nlm.nih.gov/articles/PMC11516528/
  81. https://pmc.ncbi.nlm.nih.gov/articles/PMC10535738/
  82. https://clinicaltrials.gov/study/NCT05119920
  83. https://www.mdpi.com/2075-4418/14/1/91
  84. https://clinicaltrials.gov/study/NCT04470479
  85. https://www.researchgate.net/publication/370631450_Clinical_Study_of_Efficacy_and_Safety_of_Oral_Pilocarpine_in_the_Treatment_of_Severe_Dry_Eye_Disease_International_Journal_of_Pharmaceutical_and_Clinical_Research
  86. https://www.drugs.com/pro/pilocarpine-eye-drops.html
  87. https://www.mdpi.com/2075-4418/15/3/308
  88. https://www.frontiersin.org/journals/ophthalmology/articles/10.3389/fopht.2023.1101281/full
  89. https://www.researchgate.net/publication/233816082_Pilocarpine-loaded_polyDL-lactic-co-glycolic_acid_nanoparticles_as_potential_candidates_for_controlled_drug_delivery_with_enhanced_ocular_pharmacological_response
  90. https://www.mdpi.com/1999-4923/17/8/1087
  91. https://pmc.ncbi.nlm.nih.gov/articles/PMC12037438/
  92. https://www.sciencedirect.com/science/article/pii/S240584402408633X
  93. https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1592014/full
  94. https://pmc.ncbi.nlm.nih.gov/articles/PMC7842738/
  95. https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1392977/full
  96. https://www.sciencedirect.com/science/article/abs/pii/S0149763421003699
  97. https://pmc.ncbi.nlm.nih.gov/articles/PMC9999627/
  98. https://iovs.arvojournals.org/article.aspx?articleid=2128095
  99. https://link.springer.com/article/10.1007/BF00219937
  100. https://pubmed.ncbi.nlm.nih.gov/25886199/
  101. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221832
  102. https://www.mdpi.com/1422-0067/26/19/9540
  103. https://pmc.ncbi.nlm.nih.gov/articles/PMC12081402/
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