関: echothiopate、echothiophate、echothiophate iodide、ecothiopate iodide

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/04 11:13:33」(JST)

wiki en

Echothiophate (Phospholine) is a parasympathomimetic and a phosphorothioate. It is an irreversible 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 After contacting the American Academy of Ophthalmology (AAO), Wyeth rescinded their decision and, according to AAO public relations representative Michelle Stephens, the AAO and Wyeth were in talks for about a year about manufacturing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 is made by reacting diethylchlorophosphoric acid with 2-dimethylaminoethylmercaptan, giving S-(2-dimethylaminoethyl)-O,O-diethylthiophosphate, which is alkylated by methyl iodide, forming echothiophate.^[3]

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.
^ Eurotimes article: "Echothiophate iodide shortage leaves US specialists struggling to find alternative for acute cases"
^ H.M. Fitch, U.S. Patent 2,911,430 (1959)

English Journal

Lacrimal canalicular obstruction associated with topical ocular medication.

McNab AA.SourceRoyal Victorian Eye and Ear Hospital, Melbourne, Australia. amcnab@medeserv.com.au
Australian and New Zealand journal of ophthalmology.Aust N Z J Ophthalmol.1998 Aug;26(3):219-23.
PURPOSE: To describe the association between the use of various types of topical ocular medications and acquired lacrimal canalicular obstruction in 14 patients.METHODS: The records of all patients in the author's practice with either lacrimal canalicular or punctal occlusion associated with the use
PMID 9717753

A comparison of the electrophysiological effects of two organophosphates, mipafox and ecothiopate, on mouse limb muscles.

de Blaquière GE, Williams FM, Blain PG, Kelly SS.SourceDepartment of Environmental and Occupational Medicine, University of Newcastle upon Tyne, United Kingdom.
Toxicology and applied pharmacology.Toxicol Appl Pharmacol.1998 Jun;150(2):350-60.
Adult male albino mice were given single subcutaneous injections of either mipafox (110 mumol/kg) or ecothiopate (0.5 mumol/kg), two organophosphorus compounds (OPs). Acetylcholinesterase activity was measured in the soleus (slow-twitch) and extensor digitorum longus (EDL; fast-twitch) muscles. At 7
PMID 9653066

[Prolonged apnea after administration of succinylcholine].

Pujić B, Bekvalac M, Kolak R, Ziramov J.SourceInstitut za hirurgiju, Medicinski fakultet, Vojnomedicinski centar, Novi Sad.
Medicinski pregled.Med Pregl.1998 Mar-Apr;51(3-4):178-81.
INTRODUCTION: Succinylcholine is a depolarizing muscle relaxant that has been used for five decades in clinical practice. It is decomposed by enzyme acetylcholinesterase, which is synthesized in posed by enzyme acetylcholinesterase, which is synthesized in the liver. This process lasts a few minutes
PMID 9611965

Related Pictures

★リンクテーブル★

リンク元	「echothiophate iodide」「echothiophate」「echothiopate」
拡張検索	「ecothiopate iodide」

「echothiophate iodide」

Echothiophate
Systematic (IUPAC) name
	2-(Diethoxyphosphorylsulfanyl)ethyl-N,N,N-trimethylazanium iodide
Clinical data
Trade names	Phospholine
Routes of; administration	Topical (eye drops)
Identifiers
CAS Registry 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
Molecular 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 ;
(what is this?) (verify)