Echothiophate

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 Number	6736-03-4
ATC code	S01EB03 (WHO)
PubChem	CID 10547
DrugBank	DB01057
ChemSpider	10107
UNII	0F350BVT6S
KEGG	D02193
ChEBI	CHEBI:59849
ChEMBL	CHEMBL1201341
Chemical data
Formula	C9H23INO3PS
Molar 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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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 After contacting the American Academy of Ophthalmology (AAO), Wyeth rescinded their decision and, according to AAO public relations representative Michelle Stephens, the AAO and Wyeth were in talks for about a year about manufacturing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

1. 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.
2. Eurotimes article: "Echothiophate iodide shortage leaves US specialists struggling to find alternative for acute cases"
3. H.M. Fitch, U.S. Patent 2,911,430 (1959)