cholinesterase inhibitor

コリンエステラーゼ阻害薬

関

acetylcholinesterase inhibitor、anticholinesterase、anticholinesterase agent

WordNet

1. limit, block, or decrease the action or function of; "inhibit the action of the enzyme"; "inhibit the rate of a chemical reaction"
2. control and refrain from showing; of emotions, desires, impulses, or behavior (同)bottle up, suppress
3. limit the range or extent of; "Contact between the young was inhibited by strict social customs"
4. a substance that retards or stops an activity
5. an enzyme that hydrolyses acetylcholine (into choline and acetic acid)

PrepTutorEJDIC

1. 〈感情・欲望・行動・作用など〉‘を'抑制する / (…しないように)〈人〉‘を'抑制する,妨げる《+『名』+『from』+『名』(do『ing』)》
2. 抑制する人(物) / 化学反応抑制剤

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/06/30 12:48:59」(JST)

wiki en

[Wiki en表示]

Not to be confused with ACE inhibitor.

Acetylcholine

Acetylcholinesterase

Acetylcholinesterase inhibition

An acetylcholinesterase inhibitor (often abbreviated AChEI) or anti-cholinesterase is a chemical that inhibits the acetylcholinesterase enzyme from breaking down acetylcholine, thereby increasing both the level and duration of action of the neurotransmitter acetylcholine. Reversible, quasi-irreversible (or pseudirreversible in some sources) and irreversible inhibitors exist.

Uses

Acetylcholinesterase inhibitors:

• Occur naturally as venoms and poisons
• Are used as weapons in the form of nerve agents
• Are used as insecticides
• Are used medicinally:
  • To treat myasthenia gravis. In myasthenia gravis, they are used to increase neuromuscular transmission.
  • To treat glaucoma
  • To treat Alzheimer's disease
  • To treat Lewy Body Dementia
  • To treat Postural Tachycardia Syndrome
  • As an antidote to anticholinergic poisoning
  • To reverse the effect of non-depolarising muscle relaxants
  • To treat Apathy

Adverse effects

Potential side effects of acetylcholinesterase inhibitors
mild – usually goes away	potentially serious
Diarrhea Headache Insomnia Nausea Vomiting	Abdominal pain Lack of appetite Yellowed skin Dizziness Slow heartbeat Sudden or substantial weight loss Weakness

Examples

Reversible inhibitor

Compounds which function as reversible competitive or noncompetitive inhibitors of cholinesterase are those most likely to have therapeutic uses. These include:

• Some organophosphates not listed under "Irreversible" below
• Delta9-tetrahydrocannabinol (THC)
• Carbamates
  • Physostigmine
  • Neostigmine
  • Pyridostigmine
  • Ambenonium
  • Demarcarium
  • Rivastigmine
• Phenanthrene derivatives
  • Galantamine
• Caffeine – noncompetitive (although an Adenosine receptor antagonist)
• Piperidines
  • Donepezil, also known as E2020
• Tacrine, also known as tetrahydroaminoacridine (THA')
• Edrophonium
• Huperzine A
• Ladostigil
• Ungeremine
• Lactucopicrin

Comparison table

Comparison of reversible acetylcholinesterase inhibitors

Inhibitor	Duration	Main site of action	Clinical use	Adverse effects
Edrophonium	short (10 min.)	neuromuscular junction	diagnosis of myasthenia gravis
Neostigmine	medium (1–2 hrs.)	neuromuscular junction	Reverse neuromuscular block (intravenously) Treat myasthenia gravis (orally)	visceral
Physostigmine	medium (0.5-5 hrs.)	postganglionic parasympathetic	treat glaucoma (eye drops)
Pyridostigmine	medium (2–3 hrs.)	neuromuscular junction	Treat myasthenia gravis (orally)
Dyflos	long	postganglionic parasympathetic	historically to treat glaucoma (eye drops)	toxic
Ecothiopate (irreversible)	long	postganglionic parasympathetic	treat glaucoma (eye drops)	systemic effects
Parathion (irreversible)	long	none	toxic

Quasi-irreversible inhibitor

Compounds which function as quasi-irreversible inhibitors of cholinesterase are those most likely to have use as chemical weapons or pesticides. These include:

Organophosphates Echothiophate Diisopropyl fluorophosphate Cadusafos Chlorpyrifos Cyclosarin Dichlorvos Dimethoate Metrifonate (irreversible) Sarin Soman Tabun VX VE VG VM Diazinon Malathion Parathion

Carbamates Aldicarb Bendiocarb Bufencarb Carbaryl Carbendazim Carbetamide Carbofuran Carbosulfan Chlorbufam Chloropropham Ethiofencarb Formetanate Methiocarb Methomyl Oxamyl Phenmedipham Pinmicarb Pirimicarb Propamocarb Propham Propoxur

Natural Compounds

• Huperzine A
• Galantamine
• Onchidal
• Coumarins
• Celastrus paniculatus

Effects

Some major effects of cholinesterase inhibitors:

• Actions on the parasympathetic nervous system, (the parasympathetic branch of the autonomic nervous system) may cause bradycardia, hypotension, hypersecretion, bronchoconstriction, GI tract hypermotility, and decrease intraocular pressure.
• SLUDGE syndrome.
• Actions on the neuromuscular junction will result in prolonged muscle contraction.

Administration of reversible cholinoesterase inhibitors is contraindicated with those that have urinary retention due to obstruction.

Titration phase

When used in the central nervous system to alleviate neurological symptoms, such as rivastigmine in Alzheimer's disease, all cholinesterase inhibitors require doses to be increased gradually over several weeks, and this is usually referred to as the titration phase. Many other types drug treatments may require a titration or stepping up phase. This strategy is used to build tolerance to adverse events or to reach a desired clinical effect.

See also

• Pesticide poisoning

References

External links

• Acetylcholinesterase inhibitors at the US National Library of Medicine Medical Subject Headings (MeSH)

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. 認知症治療におけるコリンエステラーゼ阻害剤 cholinesterase inhibitors in the treatment of dementia
• 2. 認知症の治療 treatment of dementia
• 3. 重症筋無力症患者に対する麻酔 anesthesia for the patient with myasthenia gravis
• 4. レビー小体型認知症の予後および治療 prognosis and treatment of dementia with lewy bodies
• 5. 有機リン剤およびカルバメート中毒 organophosphate and carbamate poisoning

English Journal

• Pharmacological treatments for neuropsychiatric symptoms of dementia in long-term care: a systematic review.

• Seitz DP, Gill SS, Herrmann N, Brisbin S, Rapoport MJ, Rines J, Wilson K, Le Clair K, Conn DK.SourceDepartment of Psychiatry, Queen's University, Kingston, Ontario, Canada.
• International psychogeriatrics / IPA.Int Psychogeriatr.2013 Feb;25(2):185-203. doi: 10.1017/S1041610212001627. Epub 2012 Oct 19.
• ABSTRACT Background: Medications are frequently prescribed for neuropsychiatric symptoms (NPS) associated with dementia, although information on the efficacy and safety of medications for NPS specifically in long-term care (LTC) settings is limited. The objective of this st
• PMID 23083438

• Kinetic and physicochemical properties of brain acetylcholinesterase from the peacock bass (Cichla ocellaris) and in vitro effect of pesticides and metal ions.

• Silva KC, Assis CR, Oliveira VM, Carvalho LB Jr, Bezerra RS.SourceDepartamento de Bioquímica and Laboratório de Imunopatologia Keizo Asami, Universidade Federal de Pernambuco, Recife-PE, Brazil.
• Aquatic toxicology (Amsterdam, Netherlands).Aquat Toxicol.2013 Jan 15;126:191-7. doi: 10.1016/j.aquatox.2012.11.001. Epub 2012 Nov 9.
• Brain acetylcholinesterase (AChE; EC 3.1.1.7) from peacock bass (Cichla ocellaris) was characterized and the effect of organophosphorus and carbamate pesticides as well as ions and heavy metals was evaluated. The kinetic parameters K(m) and V(max) were determined as 0.769mM and 0.189U/mg of protein
• PMID 23220411

• Synthesis, molecular modeling and evaluation of novel N'-2-(4-benzylpiperidin-/piperazin-1-yl)acylhydrazone derivatives as dual inhibitors for cholinesterases and Aβ aggregation.

• Ozturan Özer E, Unsal Tan O, Ozadali K, Küçükkılınç T, Balkan A, Uçar G.SourceDepartment of Biochemistry, Faculty of Medicine, Başkent University, Ankara 06530, Turkey.
• Bioorganic & medicinal chemistry letters.Bioorg Med Chem Lett.2013 Jan 15;23(2):440-3. doi: 10.1016/j.bmcl.2012.11.064. Epub 2012 Nov 28.
• To develop new drugs for treatment of Alzheimer's disease, a group of N'-2-(4-Benzylpiperidin-/piperazin-1-yl)acylhydrazones was designed, synthesized and tested for their ability to inhibit acetylcholinesterase, butyrylcholinesterase and aggregation of amyloid beta peptides (1-40, 1-42 and 1-40_1-4
• PMID 23273219

Japanese Journal

• Alzheimer病の新承認薬--その効能と限界

• 柳澤 勝彦
• Brain and nerve 63(8), 863-868, 2011-08
• NAID 40018943966

• 仰臥位高血圧・立位低血圧を伴う糖尿病性腎症血液透析患者の血圧コントロール

• 田中 勝喜,西口 健介,高折 光司,村上 徹,岸本 聡子,玉置 佐奈美,井ノ口 眞澄美,左海 佳奈子,門脇 勧,織田 浩彰,御厨 亮子,桑原 隆
• 日本透析医学会雑誌 = Journal of Japanese Society for Dialysis Therapy 44(5), 449-453, 2011-05-28
• 67歳，女性．糖尿病性腎症による血液透析歴16年．週3回3.5時間の維持透析で，体重増加は基本体重（40.2 kg）の約4％である．起床時の血圧は190/90 mmHg，透析前座位血圧120/60 mmHg，透析開始直後（仰臥位）血圧200/90 mmHgにも上昇する．透析終了後起立により血圧が90/50 mmHgまで低下し，当日はほとんど起立できない状況が続いていた．透析中の仰臥位血圧上昇につい …
• NAID 10029406867

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★リンクテーブル★

リンク元	「コリンエステラーゼ阻害薬」「anticholinesterase agent」「コリンエステラーゼ阻害剤」
拡張検索	「acetylcholinesterase inhibitor」「acetylcholinesterase inhibitors」「cholinesterase inhibitors」
関連記事	「inhibit」「inhibitor」「cholinesterase」「cholinesterases」

「コリンエステラーゼ阻害薬」

　　[★]

英

cholinesterase inhibitor cholinesterase inhibitors

同

抗コリンエステラーゼ薬 anticholinesterase

関

アセチルコリン、アセチルコリン受容体、副交感神経

コリンエステラーゼ阻害薬=

• フィゾスチグミン physostigmine
• ネオスチグミン neostigmine
• エドロフォニウム edrophonium
• ドネペジル donepezil

アルツハイマー病の治療薬

作用機序

• 図：GOO.203

活性部位に結合

• エドロフォニウムやドネペジルは活性化部位に結合して、酵素の機能を可逆的に失わせる (GOO.204)

エドロフォニウムは四級アミンなので腎臓より速やかに排泄され、持続時間が短い。

酵素ををカルバモイル化

• フィゾスチグミンやネオスチグミンは活性化部位に位置するセリン残基のヒドロキシ基にカルバモイル基(NH₂CO-)を転移することで、機能を可逆的に失わせる (GOO.204)

酵素をリン酸化

• 有機リン化合物系

臨床応用

種類	疾患への適応
ムスカリン作動薬	緑内障、手術後の腸管麻痺、尿閉
コリンエステラーゼ阻害薬	緑内障、手術後の腸管麻痺、尿閉、重症筋無力症の診断・治療、アルツハイマー病
ムスカリン受容体遮断薬	鎮痙薬（消化管、胆管、尿路など）、胃・十二指腸潰瘍、散瞳薬、パーキンソン病、麻酔前投与

「anticholinesterase agent」

　　[★]

• 抗コリンエステラーゼ薬、抗コリンエステラーゼ剤

関

acetylcholinesterase inhibitor、anticholinesterase、cholinesterase inhibitor

「コリンエステラーゼ阻害剤」

　　[★]

英

cholinesterase inhibitor

関

抗コリンエステラーゼ薬、アセチルコリンエステラーゼ阻害薬、コリンエステラーゼ阻害薬

「acetylcholinesterase inhibitor」

　　[★] アセチルコリンエステラーゼ阻害薬

「acetylcholinesterase inhibitors」

　　[★] アセチルコリンエステラーゼ阻害薬

「cholinesterase inhibitors」

　　[★] コリンエステラーゼ阻害薬

「inhibit」

　　[★]

• v.

• 抑制する、阻害する、阻止する

関

abrogate、block、depress、depression、deter、inhibition、interdict、prevent、prevention、repress、repression、restrain、restraint、suppress、suppression

　 　 　 　

「inhibitor」

　　[★]

• n.

• 阻害剤、阻害薬、抑制薬、抑制剤、(内在性物質について)インヒビター、抑制物質

関

blocker、depressant、suppressant

　 　

「cholinesterase」

　　[★] コリンエステラーゼ 　

「cholinesterases」

　　[★] コリンエステラーゼ