Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/21 18:20:57」(JST)

wiki en

Pyridostigmine is a parasympathomimetic and a reversible cholinesterase inhibitor. Since it is a quaternary amine, it is poorly absorbed in the gut and cannot penetrate across the blood–brain barrier.^[1]

It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.^[2]

Medical uses

Pyridostigmine is used to treat muscle weakness in people with myasthenia gravis and to combat the effects of curariform drug toxicity. Pyridostigmine bromide has been FDA approved for military use during combat situations as an agent to be given prior to exposure to the nerve agent Soman in order to increase survival. Used in particular during the first Gulf War, pyridostigmine bromide has been implicated as a causal factor in Gulf War syndrome.^[3]

Pyridostigmine sometimes is used to treat orthostatic hypotension.^[4] It may also be of benefit in chronic axonal polyneuropathy. ^[5]

It is also being prescribed 'off-label' for the postural tachycardia syndrome as well as complications resulting from Ehlers-Danlos Syndrome. ^[6]^[7]

Contraindications

Pyrostigmine bromide is contraindicated in cases of mechanical intestinal or urinary obstruction and should be used with caution in patients with bronchial asthma.^[8]^[9]

Side effects

Common side effects include:^[8]

Sweating
Diarrhea
Nausea
Vomiting
Abdominal cramps
Increased salivation
Tearing
Increased bronchial secretions
Constricted pupils
Facial flushing due to vasodilation
Erectile dysfunction

Mode of action

In a synapse, action potentials are conducted along motor nerves to their terminals where they initiate a Ca²⁺ influx and the release of acetylcholine (ACh). The ACh diffuses across the synaptic cleft and binds to receptors on the post synaptic membrane, causing an influx of Na⁺, resulting in depolarization. If large enough, this depolarization results in an action potential. To prevent constant stimulation once the ACh is released, an enzyme called acetylcholinesterase is present in the endplate membrane close to the receptors on the post synaptic membrane, and quickly hydrolyses ACh.

Pyridostigmine inhibits acetylcholinesterase in the synaptic cleft, thus slowing down the hydrolysis of acetylcholine. It is a quaternary carbamate inhibitor of cholinesterase that does not cross the blood–brain barrier which carbamylates about 30% of peripheral cholinesterase enzyme. The carbamylated enzyme eventually regenerates by natural hydrolysis and excess ACh levels revert to normal.

Names

Pyridostigmine bromide is available under the trade names Mestinon (Valeant Pharmaceuticals) and Regonol.

References

^ Amourette C, Lamproglou I, Barbier L, et al. (November 2009). "Gulf War illness: Effects of repeated stress and pyridostigmine treatment on blood-brain barrier permeability and cholinesterase activity in rat brain". Behavioural Brain Research 203 (2): 207–14. doi:10.1016/j.bbr.2009.05.002. PMID 19433115.
^ "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.
^ Golomb BA (March 2008). "Acetylcholinesterase inhibitors and Gulf War illnesses". Proceedings of the National Academy of Sciences of the United States of America 105 (11): 4295–300. Bibcode:2008PNAS..105.4295G. doi:10.1073/pnas.0711986105. JSTOR 25461411. PMC 2393741. PMID 18332428. Lay summary – Reuters (March 10, 2008).
^ Gales BJ, Gales MA. (2007). "Pyridostigmine in the treatment of orthostatic intolerance". Annals of Pharmacotherapy 41 (2): 314–8. doi:10.1345/aph.1H458. PMID 17284509.
^ Gales BJ, Gales MA (February 2007). "Pyridostigmine in the treatment of orthostatic intolerance". The Annals of Pharmacotherapy 41 (2): 314–8. doi:10.1345/aph.1H458. PMID 17284509.
^ Kanjwal K, Karabin B, Sheikh M, et al. (June 2011). "Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience". Pacing and Clinical Electrophysiology 34 (6): 750–5. doi:10.1111/j.1540-8159.2011.03047.x. PMID 21410722.
^ Gales BJ, Gales MA (February 2007). "Pyridostigmine in the treatment of orthostatic intolerance". The Annals of Pharmacotherapy 41 (2): 314–8. doi:10.1345/aph.1H458. PMID 17284509.
^ ^a ^b Mestinon | Home
^ Mestinon Official FDA information, side effects and uses

Related publications

Brenner, G. M. (2000). Pharmacology. Philadelphia, PA: W.B. Saunders Company. ISBN 0-7216-7757-6
Canadian Pharmacists Association (2000). Compendium of Pharmaceuticals and Specialties (25th ed.). Toronto, ON: Webcom. ISBN 0-919115-76-4
Neal, M.J. (2002). Medical Pharmacology at a Glance (5th ed.). London, England: Blackwell Publishing. ISBN 1-4051-3360-0

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

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. I群抗不整脈薬の主な副作用 major side effects of class i antiarrhythmic drugs
3. 起立性低血圧および食後低血圧の治療 treatment of orthostatic and postprandial hypotension
4. 重症筋無力症の治療 treatment of myasthenia gravis
5. 抗コリン剤中毒 anticholinergic poisoning

English Journal

A Novel Method Aimed at Counteracting the Side Effects Caused by Prostaglandin E2 Deficiency during Non-Steroidal Anti-Inflammatory Drug Therapy.

Gargaun S, Gargaun L.Author information Medical Development Director, Selag Inc. 203-105 La Rose Ave Toronto, Ontario, M9P 1A9 Canada. lgargaun@gmail.com.AbstractBackground: Prostaglandin E2 (PGE2) plays key physiological roles within the body's organs and the systemic environment. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the biosynthesis of PGE2, which can lead to global PGE2 deficiency, resulting in serious side effects in the gastrointestinal, renal and other systems. In contrast, various pyridine derivatives have been found to increase endogenous PGE2 levels within multiple organs and the systemic environment. We hypothesised that the use of pyridine derivatives (nicotinic acid, nicotinyl alcohol, pyridinol carbamate, pyridoxine hydrochloride and pyridostigmine bromide) can recover PGE2 levels during NSAID treatment. Methods: Reassessment of experimental data on PGE2 levels in NSAIDs and pyridine derivatives treatment, and in controls from four previously published, independent studies. Results: Overall, in all our investigations P values for unpaired or pair-wise comparisons were not statistically significant. This finding is based on both in vitro studies using animal and human tissues and in vivo studies performed with healthy volunteers. Conclusions: We demonstrated that using pyridine derivatives along with NSAIDs, such as nonselective cyclooxygenase (COX) and selective COX-2 inhibitors, does not reduce endogenous PGE2 expression to below basal levels. Using pyridine derivatives to correct a PGE2 deficiency during NSAID treatment is a novel method that we propose can offer a valuable, cost-effective therapeutic approach to preventing and treating the side effects of NSAIDs.
Anti-inflammatory & anti-allergy agents in medicinal chemistry.Antiinflamm Antiallergy Agents Med Chem.2013 Dec 29. [Epub ahead of print]
Background: Prostaglandin E2 (PGE2) plays key physiological roles within the body's organs and the systemic environment. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the biosynthesis of PGE2, which can lead to global PGE2 deficiency, resulting in serious side effects in the gastrointestina
PMID 24383936

Persistent Na+ and K+ channel dysfunctions after chronic exposure to insecticides and pyridostigmine bromide.

Nutter TJ, Jiang N, Cooper BY.Author information Division of Neuroscience, Dept. of Oral and Maxillofacial Surgery, JHMHC, University of Florida College of Dentistry, Box 100416, Gainesville, FL 32610, United States. Electronic address: tnutter@dental.ufl.edu.AbstractMany soldiers that served in the 1991 Gulf War developed widespread chronic pain. Exposure to insecticides and the nerve gas prophylactic pyridostigmine bromide (PB) was identified as risk factors by the Research Advisory Committee on Gulf War Veterans' Illnesses (GWI). We examined whether a 60 day exposure to neurotoxicants/PB (NTPB) produced behavioral, molecular and cellular indices of chronic pain in the rat. Male rats were exposed to chlorpyrifos (120mg/kg; SC), permethrin (2.6mg/kg; topical), and PB (13.0mg/kg; oral) or their respective vehicles (corn oil, ethanol, and water). Permethrin can exert profound influences on voltage activated Na(+) channel proteins; while chlorpyrifos and PB can increase absorption and/or retard metabolism of permethrin as well as inhibit cholinesterases. During and after exposure to these agents, we assessed muscle pressure pain thresholds and activity (distance and rest time). Eight and 12 weeks after treatments ceased, we used whole cell patch electrophysiology to examine the physiology of tissue specific DRG nociceptor channel proteins expressed in muscle and putative vascular nociceptors (voltage dependent, activation, inactivation, and deactivation). Behavioral indices were unchanged after treatment with NTPB. Eight weeks after treatments ended, the peak and average conductance of Kv7 mediated K(+) currents were significantly increased in vascular nociceptors. When a specific Kv7 inhibitor was applied (linopirdine, 10μM) NTPB treated vascular nociceptors emitted significantly more spontaneous APs than vehicle treated neurons. Changes to Kv7 channel physiology were resolved 12 weeks after treatment. The molecular alterations to Kv7 channel proteins and the specific susceptibility of the vascular nociceptor population could be important for the etiology of GWI pain.
Neurotoxicology.Neurotoxicology.2013 Dec;39:72-83. doi: 10.1016/j.neuro.2013.08.006. Epub 2013 Aug 29.
Many soldiers that served in the 1991 Gulf War developed widespread chronic pain. Exposure to insecticides and the nerve gas prophylactic pyridostigmine bromide (PB) was identified as risk factors by the Research Advisory Committee on Gulf War Veterans' Illnesses (GWI). We examined whether a 60 day
PMID 23994030

Mood and memory deficits in a model of Gulf War illness are linked with reduced neurogenesis, partial neuron loss, and mild inflammation in the hippocampus.

Parihar VK, Hattiangady B, Shuai B, Shetty AK.Author information 1] Research Service, Durham Veterans Affairs Medical Center, Durham, NC, USA [2] Department of Surgery (Neurosurgery), Duke University Medical Center, Durham, NC, USA.AbstractImpairments in mood and cognitive function are the key brain abnormalities observed in Gulf war illness (GWI), a chronic multisymptom health problem afflicting ∼25% of veterans who served in the Persian Gulf War-1. Although the precise cause of GWI is still unknown, combined exposure to a nerve gas prophylaxis drug pyridostigmine bromide (PB) and pesticides DEET and permethrin during the war has been proposed as one of the foremost causes of GWI. We investigated the effect of 4 weeks of exposure to Gulf war illness-related (GWIR) chemicals in the absence or presence of mild stress on mood and cognitive function, dentate gyrus neurogenesis, and neurons, microglia, and astrocytes in the hippocampus. Combined exposure to low doses of GWIR chemicals PB, DEET, and permethrin induced depressive- and anxiety-like behavior and spatial learning and memory dysfunction. Application of mild stress in the period of exposure to chemicals exacerbated the extent of mood and cognitive dysfunction. Furthermore, these behavioral impairments were associated with reduced hippocampal volume and multiple cellular alterations such as chronic reductions in neural stem cell activity and neurogenesis, partial loss of principal neurons, and mild inflammation comprising sporadic occurrence of activated microglia and significant hypertrophy of astrocytes. The results show the first evidence of an association between mood and cognitive dysfunction and hippocampal pathology epitomized by decreased neurogenesis, partial loss of principal neurons, and mild inflammation in a model of GWI. Hence, treatment strategies that are efficacious for enhancing neurogenesis and suppressing inflammation may be helpful for alleviation of mood and cognitive dysfunction observed in GWI.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.Neuropsychopharmacology.2013 Nov;38(12):2348-62. doi: 10.1038/npp.2013.158. Epub 2013 Jun 28.
Impairments in mood and cognitive function are the key brain abnormalities observed in Gulf war illness (GWI), a chronic multisymptom health problem afflicting ∼25% of veterans who served in the Persian Gulf War-1. Although the precise cause of GWI is still unknown, combined exposure to a nerve ga
PMID 23807240

Japanese Journal

咀嚼困難を契機に重症筋無力症と診断された高齢者の1例

齊藤美香,山口雅庸
日本口腔外科学会雑誌 60(1), 12-16, 2014
… Oral treatment with mestinon was initiated; …
NAID 130005064963

胸せんしゅと種々の免疫異常を合併した重症筋無力症の経過中に比較的急性に発症した赤芽球ろうの１剖検例

井上敦,池田修一,高昌星,柳沢信夫,長沼邦明,中畑龍俊
日本内科学会雑誌 73(6), 817-824, 1984
… てwaning,抗Ach受容体抗体高値および胸部CTで胸腺腫陰影があり,胸腺腫を伴つた重症筋無力症と診断.またこの時抗核抗体,抗サイログロブリン抗体,抗マイクロゾーム抗体の高値も認めた.以後pyridostigmin bromide薬(Mestinon) 180mg/dにて外来で経過観察.昭和57年2月より約1カ月の経過でRBC 98万, Hb 2.7g/dlと著しい貧血が出現,末梢血および骨髄像より赤芽球癆と診断,ステロイド剤と免疫抑制剤の使用により貧血は改善したが全身の感染 …
NAID 130000891279

泌尿器科領域における3-dimethyl carbamoylexy-1-methyl pyridinium bromide(Mestinon)の使用経験

佐々木秀平 [他],沼里進,高橋崎三,赤坂俊幸,久保隆,大堀勉
泌尿器科紀要 20(7), 483-488, 1974-07
… Mestinon was administered to 25 patients with neurogenic bladder and 3 with prostatic hypertrophy at daily dose of 180 mg (t.i.d.) for consecutive 2 to 51 days. …
NAID 120002232823

Related Pictures

Name : MESTINON TABLET 60 MG Mestinon - Liga Myasthenia Gravis vzw Mestinon, Mestinon opinie, Mestinon ulotka MESTINON tbl 150X 60mg Mestinon ® MESTINON® (pyridostigmine bromide) SYRUP Nombre Comercial: Mestinon Principio MEDA - Mestinon Valeant

★リンクテーブル★

リンク元	「ピリドスチグミン」「pyridostigmine」

「ピリドスチグミン」

Pyridostigmine
Systematic (IUPAC) name
	3-[(dimethylcarbamoyl)oxy]-1-methylpyridinium
Clinical data
Trade names	Mestinon
AHFS/Drugs.com	monograph
MedlinePlus	a682229
Pregnancy; category	AU: C; US: C (Risk not ruled out); ;
Legal status	UK: POM (Prescription only); US: ℞-only;
Routes of; administration	Oral, intravenous
Pharmacokinetic data
Bioavailability	7.6 +/- 2.4%
Biological half-life	1.78 +/- 0.24hrs
Excretion	Renal
Identifiers
CAS Number	155-97-5
ATC code	N07AA02
PubChem	CID: 4991
DrugBank	DB00545
ChemSpider	4817
UNII	19QM69HH21
KEGG	D00487
ChEMBL	CHEMBL1115
Chemical data
Formula	C9H13N2O2
Molecular mass	181.212 g/mol
	SMILES O=C(Oc1ccc[n+](c1)C)N(C)C ;
	InChI InChI=1S/C9H13N2O2/c1-10(2)9(12)13-8-5-4-6-11(3)7-8/h4-7H,1-3H3/q+1 ; Key:RVOLLAQWKVFTGE-UHFFFAOYSA-N ;
(verify)

　　[★]

英: pyridostigmine
化: 臭化ピリドスチグミン pyridostigmine bromide
商: Mestinon メスチノン
関: 重症筋無力症

「pyridostigmine」

　　[★] ピリドスチグミン

同: Mestinon

[pmid19433115-1] Amourette C, Lamproglou I, Barbier L, et al. (November 2009). "Gulf War illness: Effects of repeated stress and pyridostigmine treatment on blood-brain barrier permeability and cholinesterase activity in rat brain". Behavioural Brain Research 203 (2): 207–14. doi:10.1016/j.bbr.2009.05.002. PMID 19433115.

[WHO2015E-2] "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.

[Golomb-3] Golomb BA (March 2008). "Acetylcholinesterase inhibitors and Gulf War illnesses". Proceedings of the National Academy of Sciences of the United States of America 105 (11): 4295–300. Bibcode:2008PNAS..105.4295G. doi:10.1073/pnas.0711986105. JSTOR 25461411. PMC 2393741. PMID 18332428. Lay summary – Reuters (March 10, 2008).

[Gales-2007-4] Gales BJ, Gales MA. (2007). "Pyridostigmine in the treatment of orthostatic intolerance". Annals of Pharmacotherapy 41 (2): 314–8. doi:10.1345/aph.1H458. PMID 17284509.

[Galassi-2011-5] Gales BJ, Gales MA (February 2007). "Pyridostigmine in the treatment of orthostatic intolerance". The Annals of Pharmacotherapy 41 (2): 314–8. doi:10.1345/aph.1H458. PMID 17284509.

[6] Kanjwal K, Karabin B, Sheikh M, et al. (June 2011). "Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience". Pacing and Clinical Electrophysiology 34 (6): 750–5. doi:10.1111/j.1540-8159.2011.03047.x. PMID 21410722.

[7] Gales BJ, Gales MA (February 2007). "Pyridostigmine in the treatment of orthostatic intolerance". The Annals of Pharmacotherapy 41 (2): 314–8. doi:10.1345/aph.1H458. PMID 17284509.

[autogenerated1-8] Mestinon | Home

[9] Mestinon Official FDA information, side effects and uses

匿名

検索

案内

案内

Mestinon