WordNet

a complex consisting of an organic base in association with hydrogen chloride
cholinergic alkaloid used in eyedrops to treat glaucoma

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/10/04 14:38:34」(JST)

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Pilocarpine is a drug used to treat dry mouth and glaucoma. It is a parasympathomimetic alkaloid obtained from the leaves of tropical South American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist^[2] in the parasympathetic nervous system, which acts therapeutically at the muscarinic acetylcholine receptor M₃ due to its topical application,^[3] e.g., in glaucoma and xerostomia.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.^[4]

Medical uses

Pilocarpine stimulates the secretion of large amounts of saliva and sweat.^[5] It is used to treat dry mouth (xerostomia), particularly in Sjögren's syndrome, but also as a side effect of radiation therapy for head and neck cancer.

It has also been used in the treatment of chronic open-angle glaucoma and acute angle-closure glaucoma for over 100 years.^[6] 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.

In ophthalmology, pilocarpine is also used to reduce the possibility of 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, relieving these symptoms. The most common concentration for this use is pilocarpine 1%, the weakest concentration.

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.

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 secretion, bronchospasm, bradycardia, vasodilation, and diarrhea. Eye drops can result in brow ache and chronic use in miosis.

Systemic injection of pilocarpine can compromise the blood brain barrier allowing pilocarpine to gain access to the brain which can lead to chronic epilepsy. Epilepsy induced by injected pilocarpine has been used to develop animal models in rodents in order to study human epilepsy.

"Scoline apnea" is a serious complication. In that condition, patient is unable to resume normal respiration after termination of general anesthesia.

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.^[7]

Pilocarpine is extracted from the powdered leaf material in a multi-step process. First the material is treated with ethanol acidified with hydrochloric acid, and the solvents removed under reduced pressure. The resultant aqueous residue is neutralized with ammonia and put aside until the resin has completely settled. It is then filtered and concentrated by sugar solution to a small volume, made alkaline with ammonia, and finally extracted with chloroform. The solvent is removed under reduced pressure.^{[verification needed]}

Scientific

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.^[8] Smaller doses may be used to induce salivation in order to collect samples of saliva, for instance, to obtain information about IgA 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 xylazine.

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).

References

^ Mervyn Gornitsky; George Shenouda; Khalil Sultanem; Howard Katz; Michael Hier; Martin Black; Ana M Velly (2004). "Double-blind randomized, placebo-controlled study of pilocarpine to salvage salivary gland function during radiotherapy of patients with head and neck cancer". Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology. 98 (1): 45–52.
^ Tracy A. Spalding; Carol Trotter; Niels Skjaerbaek; Terri L. Messier; Erika A. Currier; Ethan S. Burstein; Donghui Li; Uli Hacksell; Mark R. Brann (2002). "Discovery of an Ectopic Activation Site on the M1 Muscarinic Receptor". Molecular Pharmacology. 61 (6): 1297–1302.
^ Pharmacology, (Rang, Dale, Ritter & Moore, ISBN 0-443-07145-4, 5th ed., Churchill Livingstone 2003) p. 144.
^ "WHO Model List of Essential Medicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
^ "Pilocarpine".
^ Rosin, A. (1991). "Pilocarpine. A miotic of choice in the treatment of glaucoma has passed 110 years of use". Oftalmologia. Romania. 35 (1): 53–55. PMID 1811739.
^ De Abreu, Ilka Nacif; Sawaya, Alexandra Cristine H. F.; Eberlin, Marcos Nogueira; Mazzafera, Paulo (November–December 2005). "Production of Pilocarpine in Callus of Jaborandi (Pilocarpus microphyllus Stapf)". In Vitro Cellular & Developmental Biology. Plant. Society for In Vitro Biology. 41 (6): 806–811.
^ Morimoto, K; Fahnestock, M; Racine, RJ (May 2004). "Kindling and status epilepticus models of epilepsy: rewiring the brain.". Progress in neurobiology. 73 (1): 1–60. doi:10.1016/j.pneurobio.2004.03.009. PMID 15193778.

External links

U.S. National Library of Medicine: Drug Information Portal - Pilocarpine

UpToDate Contents

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1. シェーグレン症候群における口内乾燥およびその他の非眼結膜炎症状の治療 treatment of dry mouth and other non ocular sicca symptoms in sjogrens syndrome
2. 頭頚部癌の後期合併症のマネージメントおよびその治療 management of late complications of head and neck cancer and its treatment
3. 緊張性瞳孔 tonic pupil
4. 閉塞隅角緑内障 angle closure glaucoma
5. 関節リウマチの眼症状 ocular manifestations of rheumatoid arthritis

English Journal

The effects of sleep deprivation on microRNA expression in rats submitted to pilocarpine-induced status epilepticus.

Matos G1, Scorza FA2, Mazzotti DR1, Guindalini C1, Cavalheiro EA2, Tufik S1, Andersen ML3.Author information 1Departamento de Psicobiologia, Universidade Federal de São Paulo, Brazil.2Departamento de Neurologia Experimental, Universidade Federal de São Paulo, Brazil.3Departamento de Psicobiologia, Universidade Federal de São Paulo, Brazil. Electronic address: ml.andersen12@gmail.com.AbstractEpilepsy is a neurological disorder with significant prevalence and the individuals affected by this disease have a great probability of occurrence of a lethal phenomenon known as Sudden Unexpected Death in Epilepsy (SUDEP). SUDEP occurs mainly during the night and probably during sleep. The pathophysiological mechanisms involved in this lethal phenomenon are still obscure and new evidences that could corroborate in this area are warranted. Thus, the aim of the present study was to evaluate the effect of sleep deprivation in the expression of microRNA (miRNA) in the frontal cortex and heart tissues of adult male rats after 50days of saline (SAL) or pilocarpine-induced status epilepticus (PILO). Initially 389 miRNA expressions were evaluated between SAL and PILO groups by microarray. Subsequently, 3 differentially expressed miRNAs of each tissue were investigated after total sleep deprivation (TSD 6h) and paradoxical sleep deprivation (PSD 24h). Still, it was analyzed that the effects of sleep rebound with equivalent duration of PSD and TSD. There was a significant increase of miR-146a expression, an important inflammatory modulator in the frontal cortex of PILO rats when compared to SAL animals. Animals treated with pilocarpine were affected by TSD (through overexpression of miRNAs related to inflammatory process) and these changes were maintained even after a sleep window of 6h. In contrast, miRNAs associated with heart diseases were down-regulated in PSD rebound, suggesting a possible restoration of homeostasis in cardiovascular system of SAL and PILO groups.
Progress in neuro-psychopharmacology & biological psychiatry.Prog Neuropsychopharmacol Biol Psychiatry.2014 Jun 3;51:159-65. doi: 10.1016/j.pnpbp.2014.02.001. Epub 2014 Feb 11.
Epilepsy is a neurological disorder with significant prevalence and the individuals affected by this disease have a great probability of occurrence of a lethal phenomenon known as Sudden Unexpected Death in Epilepsy (SUDEP). SUDEP occurs mainly during the night and probably during sleep. The pathoph
PMID 24530830

Synchronous alteration pattern between serine-threonine kinase receptor-associated protein and Smad7 in pilocarpine-induced rats of epilepsy.

Liu W1, Shi R, Yang W, Zhao N, Du Y, Zou Y, Yu W.Author information 1Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016, China.AbstractPurpose: Recent studies have shown that transforming growth factor β (TGFβ) signaling participates in the epileptogenesis. Serine-threonine kinase receptor-associated protein (STRAP) and Smad7 synergize in the inhibition of the TGFβ signaling. The aim of the present study was to determine the expression pattern of STRAP and Smad7 in the hippocampus and temporal lobe cortex of pilocarpine-induced rats models of epilepsy. Methods: Lithium chloride-pilocarpine-induced rats with status epilepticus (SE) were established. Total of 60 male Sprague-Dawley rats was used as control (n = 10), 24 h (n = 10), 72 h (n = 10), 1 week (n = 10), 1 month (n = 10), and 2 months (n = 10) after pilocarpine-induced SE, respectively. We detected the expression levels of STRAP and Smad7 in the hippocampus and temporal lobe cortex of rats at the aforementioned time points using western blotting and immunohistochemistry. Results: STRAP level was significantly decreased in 24 h, 72 h (acute stage), 1 week (latent stage), 1 month, 2 months (chronic stage), respectively, in the rat models compared with the control rats by using both western blotting and immunohistochemistry. Smad7 had similar reduced pattern as STRAP. Conclusions: Our results indicate that STRAP and Smad7 proteins might be involved in the development of temporal lobe epilepsy. Synapse 68:275-282, 2014. © 2014 Wiley Periodicals, Inc.
Synapse (New York, N.Y.).Synapse.2014 Jun;68(6):275-82. doi: 10.1002/syn.21739. Epub 2014 Mar 11.
Purpose: Recent studies have shown that transforming growth factor β (TGFβ) signaling participates in the epileptogenesis. Serine-threonine kinase receptor-associated protein (STRAP) and Smad7 synergize in the inhibition of the TGFβ signaling. The aim of the present study was to determine the exp
PMID 24577865

NK1 receptors antagonism of dorsal hippocampus counteract the anxiogenic-like effects induced by pilocarpine in non-convulsive Wistar rats.

Duarte FS1, Hoeller AA2, Duzzioni M3, Gavioli EC4, Canteras NS5, De Lima TC6.Author information 1Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, PE 50670-901, Brazil.2Postgraduate Program in Medical Science, Center of Health Sciences, University Hospital, Federal University of Santa Catarina, Florianópolis, SC 88040-970, Brazil; Department of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, SC 88049-900, Brazil.3Institute of Biological Sciences and Health, Federal University of Alagoas, Maceió, AL 57020-720, Brazil.4Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN 59072-970, Brazil.5Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil.6Department of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, SC 88049-900, Brazil. Electronic address: thereza.lima@ufsc.br.AbstractRecent evidence supports a role for the substance P (SP) in the control of anxiety and epilepsy disorders. Aversive stimuli alter SP levels and SP immunoreactivity in limbic regions, suggesting that changes in SP-NK1 receptor signaling may modulate the neuronal excitability involved in seizures and anxiogenesis. The involvement of NK1 receptors of the dorsal hippocampus and lateral septum in the anxiogenic-like effects induced by a single injection of pilocarpine (PILO) was examined in non-convulsive rats evaluated in the elevated plus-maze (EPM). Male Wistar rats were systemically injected with methyl-scopolamine (1mg/kg) followed 30min later by saline or PILO (350mg/kg) and only rats that did not present status epilepticus were used. One month later, vehicle or FK888 (100pmol) - an NK1 receptor antagonist - were infused in the dorsal hippocampus or the lateral septum of the rats and then behaviorally evaluated in the EPM. Previous treatment with PILO decreased the time spent in and the frequency of entries in the open arms of the EPM, besides altering risk-assessment behaviors such as the number of unprotected head-dipping, protected stretch-attend postures and the frequency of open-arms end activity, showing thus a long-lasting anxiogenic-like profile. FK888 did not show any effect per se but inhibited the anxiogenic responses induced by PILO when injected into the dorsal hippocampus, but not into the lateral septum. Our data suggest that SP-NK1 receptor signaling of the dorsal hippocampus is involved in the anxiogenic-like profile induced by PILO in rats evaluated in the EPM test.
Behavioural brain research.Behav Brain Res.2014 May 15;265:53-60. doi: 10.1016/j.bbr.2014.01.050. Epub 2014 Feb 7.
Recent evidence supports a role for the substance P (SP) in the control of anxiety and epilepsy disorders. Aversive stimuli alter SP levels and SP immunoreactivity in limbic regions, suggesting that changes in SP-NK1 receptor signaling may modulate the neuronal excitability involved in seizures and
PMID 24512769

Japanese Journal

Efficacy and safety of orally administered pilocarpine hydrochloride for patients with juvenile-onset Sjogren's syndrome

TOMIITA Minako,TAKEI Syuji,KUWADA Naomi,NONAKA Yukiko,SAITO Kimiyuki,SHIMOJO Naoki,KOHNO Yoichi
Modern rheumatology 20(5), 486-490, 2010-10-01
NAID 10027647085

ピロカルピン塩酸塩の副作用軽減法に関する研究 : 少量多分割投与療法による多汗軽減の可能性

岩渕博史,岩渕絵美,内山公男,藤林孝司
日本口腔粘膜学会雑誌 = Journal of Japanese Society for Oral Mucous Membrane 16(1), 17-23, 2010-06-30
NAID 10029373516

★リンクテーブル★

リンク元	「ピロカルピン」
関連記事	「hydrochloride」

「ピロカルピン」

Pilocarpine
Systematic (IUPAC) name
	(3S,4R)-3-Ethyl-4-((1-methyl-1H-imidazol-5-yl)methyl)dihydrofuran-2(3H)-one
Clinical data
Trade names	Salagen
AHFS/Drugs.com	Monograph
MedlinePlus	a608039
Pregnancy; category	AU: B3; US: C (Risk not ruled out); ;
Routes of; administration	topical (eye drops), per os
Legal status
Legal status	AU: S4 (Prescription only); UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Biological half-life	0.76 hours (5 mg), 1.35 hours (10 mg)
Excretion	urine
Identifiers
CAS Number	92-13-7 ; 54-71-7 (hydrochloride)
ATC code	N07AX01 (WHO) S01EB01 (WHO)
PubChem	CID 5910
IUPHAR/BPS	305
DrugBank	DB01085
ChemSpider	5699
UNII	01MI4Q9DI3
KEGG	D00525
ChEBI	CHEBI:8207
ChEMBL	CHEMBL550
Chemical data
Formula	C11H16N2O2
Molar mass	208.257 g/mol
	SMILES O=C2OC[C@H](Cc1n(cnc1)C)[C@@H]2CC ;
	InChI 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 ; Key:QCHFTSOMWOSFHM-WPRPVWTQSA-N ;
(verify)

　　[★]

英: pilocarpine
化: 塩酸ピロカルピン pilocarpine hydrochloride
商: アドソルボカルピン、サラジェン、サンピロ、ピロリナ
関: ムスカリン受容体

muscarinic receptor agonist
アルカロイド
シェーグレン症候群や放射線照射後のxerostomia(dry mouse)に対する治療薬として用いられる(PPC.121)

「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド　

[1] Mervyn Gornitsky; George Shenouda; Khalil Sultanem; Howard Katz; Michael Hier; Martin Black; Ana M Velly (2004). "Double-blind randomized, placebo-controlled study of pilocarpine to salvage salivary gland function during radiotherapy of patients with head and neck cancer". Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology. 98 (1): 45–52.

[2] Tracy A. Spalding; Carol Trotter; Niels Skjaerbaek; Terri L. Messier; Erika A. Currier; Ethan S. Burstein; Donghui Li; Uli Hacksell; Mark R. Brann (2002). "Discovery of an Ectopic Activation Site on the M1 Muscarinic Receptor". Molecular Pharmacology. 61 (6): 1297–1302.

[Rang-3] Pharmacology, (Rang, Dale, Ritter & Moore, ISBN 0-443-07145-4, 5th ed., Churchill Livingstone 2003) p. 144.

[4] "WHO Model List of Essential Medicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.

[5] "Pilocarpine".

[6] Rosin, A. (1991). "Pilocarpine. A miotic of choice in the treatment of glaucoma has passed 110 years of use". Oftalmologia. Romania. 35 (1): 53–55. PMID 1811739.

[ivcdb-7] De Abreu, Ilka Nacif; Sawaya, Alexandra Cristine H. F.; Eberlin, Marcos Nogueira; Mazzafera, Paulo (November–December 2005). "Production of Pilocarpine in Callus of Jaborandi (Pilocarpus microphyllus Stapf)". In Vitro Cellular & Developmental Biology. Plant. Society for In Vitro Biology. 41 (6): 806–811.

[8] Morimoto, K; Fahnestock, M; Racine, RJ (May 2004). "Kindling and status epilepticus models of epilepsy: rewiring the brain.". Progress in neurobiology. 73 (1): 1–60. doi:10.1016/j.pneurobio.2004.03.009. PMID 15193778.

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案内

pilocarpine hydrochloride