関: echothiopate、echothiophate iodide、ecothiopate、ecothiopate iodide

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/12/25 19:50:08」(JST)

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Echothiophate (Phospholine) is a parasympathomimetic and a phosphorothioate. It is an acetylcholinesterase inhibitor.^[1]

Uses

It is used as an ocular antihypertensive in the treatment of chronic glaucoma and, in some cases, accommodative esotropia. It is available under several trade names such as Phospholine Iodide (Wyeth-Ayerst).

Echothiophate binds irreversibly to cholinesterase. Because of the very slow rate at which echothiophate is hydrolyzed by cholinesterase, its effects can last a week or more. Adverse effects include muscle spasm and other systemic effects.

Mechanism of action

It covalently binds by its phosphate group to serine group at the active site of the cholinesterase. Once bound, the enzyme is permanently inactive and the cell has to make new enzymes.

Shortage

Wyeth Pharmaceuticals stopped manufacturing echothiophate iodide in the US in 2003. After contacting the American Academy of Ophthalmology (AAO), Wyeth rescinded their decision and, according to AAO public relations representative Michelle Stephens, the AAO and Wyeth were in talks for about a year about manufacturing it. ^[2]

In the meantime, a worldwide shortage of the drug has occurred.

Chemistry

Echothiophate, S-(2-trimethylaminoethyl)-O,O-diethylthiophosphate, is made by reacting diethylchlorophosphoric acid with 2-dimethylaminoethylmercaptane, giving S-(2-dimethylaminoethyl)-O,O-diethylthiophosphate, which is alkylated by methyl iodide, forming echothiophate. H.M. Fitch, U.S. Patent 2,911,430 (1959).

References

^ Gabelt BT, Hennes EA, Seeman JL, Tian B, Kaufman PL (August 2004). "H-7 effect on outflow facility after trabecular obstruction following long-term echothiophate treatment in monkeys". Invest. Ophthalmol. Vis. Sci. 45 (8): 2732–6. doi:10.1167/iovs.04-0083. PMID 15277498. http://www.iovs.org/cgi/pmidlookup?view=long&pmid=15277498.
^ Eurotimes article: "Echothiophate iodide shortage leaves US specialists struggling to find alternative for acute cases"

UpToDate Contents

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1. 原発性乳児緑内障 primary infantile glaucoma
2. 小児における水平斜視の原因 causes of horizontal strabismus in children
3. 有機リン剤およびカルバメート中毒 organophosphate and carbamate poisoning

English Journal

Gene-delivered butyrylcholinesterase is prophylactic against the toxicity of chemical warfare nerve agents and organophosphorus compounds.

Parikh K, Duysen EG, Snow B, Jensen NS, Manne V, Lockridge O, Chilukuri N.SourcePhysiology and Immunology Branch, and Collaborative Research Facility, Research Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5400, USA.
The Journal of pharmacology and experimental therapeutics.J Pharmacol Exp Ther.2011 Apr;337(1):92-101. Epub 2010 Dec 28.
Gene delivery using an adenoviral system has been effective in introducing therapeutic proteins in vitro and in vivo. This study tested the feasibility of using adenovirus to deliver clinically relevant amounts of butyrylcholinesterase (BChE), a proven bioscavenger of nerve agents. The adenovirus co
PMID 21205915

Hydrolysis of organophosphate compounds by mutant butyrylcholinesterase: a story of two histidines.

Amitay M, Shurki A.SourceInstitute for Drug Research, The Lise Meitner-Minerva Center for Computational Quantum Chemistry and David R Bloom Center for Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel. avitalsh@ekmd.huji.ac.il
Proteins.Proteins.2011 Feb;79(2):352-64.
This study is aimed at understanding the hydrolysis mechanism of organophosphate (OP) compounds by G117H-BChE. It is a theoretical study that focuses on the role of the G117H mutation in the dephosphorylation step. Various proposed mechanisms are examined. We show that His117 acts as a general base
PMID 21064131

Japanese Journal

市販点眼薬の微生物汚染について

布施昌孝,片倉道啓,佐藤百合子,吉田義孝,照井和幸,福島豁行,鈴木彰
病院薬学 4(2), 70-73, 1978-08-20
… It was found that the following 3 ophthalmic solutions were contaminated with Candida Krusei, Escherichia coli, Staphylococcus epidermidis and Gaffkya tetragena : Catalin, phospholine Iodide (Echothiophate Iodide) and Artificial Tear. …
NAID 110001797913

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リンク元	「エコチオパート」「ecothiopate iodide」「ecothiopate」「echothiopate」「エコチオファート」
拡張検索	「echothiophate iodide」

「エコチオパート」

Echothiophate
Systematic (IUPAC) name
	2-(Diethoxyphosphorylsulfanyl)ethyl-N,N,N-trimethylazanium iodide
Clinical data
Trade names	Phospholine
Pregnancy cat.	?
Legal status	?
Routes	Topical (eye drops)
Identifiers
CAS number	6736-03-4
ATC code	S01EB03
PubChem	CID 10547
DrugBank	DB01057
ChemSpider	10107
UNII	0F350BVT6S
KEGG	D02193
ChEBI	CHEBI:59849
ChEMBL	CHEMBL1201341
Chemical data
Formula	C9H23INO3PS
Mol. mass	383.228 g/mol
	SMILES [I-].O=P(OCC)(OCC)SCC[N+](C)(C)C;
	InChI InChI=1S/C9H23NO3PS.HI/c1-6-12-14(11,13-7-2)15-9-8-10(3,4)5;/h6-9H2,1-5H3;1H/q+1;/p-1 ; Key:OVXQHPWHMXOFRD-UHFFFAOYSA-M ;
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