Echothiophate

Echothiophate

File:Echothiophate iodide.svg
File:Echothiophate-Molecule-3D-balls.png
Clinical data
Trade names	Phospholine
Routes of administration	Topical (eye drops)
ATC code	S01EB03 (WHO)
Identifiers
IUPAC name 2-(Diethoxyphosphorylsulfanyl)ethyl-N,N,N-trimethylazanium iodide
CAS Number	6736-03-4 checkY
PubChem CID	10547
DrugBank	DB01057 checkY
ChemSpider	10107 checkY
UNII	0F350BVT6S
KEGG	D02193 checkY
ChEBI	CHEBI:59849 checkY
ChEMBL	ChEMBL1201341 ☒N
E number	{{#property:P628}}
CompTox Dashboard (EPA)	{{#property:P3117}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C9H23INO3PS
Molar mass	383.23 g·mol−1
3D model (JSmol)	Interactive image
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 checkY Key:OVXQHPWHMXOFRD-UHFFFAOYSA-M checkY
☒NcheckY (what is this?)  (verify)

Echothiophate (Phospholine) is an irreversible acetylcholinesterase inhibitor.

Uses

It is used as an ocular antihypertensive in the treatment of open angle 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 After contacting the American Academy of Ophthalmology (AAO), Wyeth rescinded their decision and, according to AAO public relations representative Michelle Stephens, the AAO and Wyeth were in talks for about a year about manufacturing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.

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.

File:Echothiophate synthesis.png