Echothiophate (Phospholine) is an irreversible

acetylcholinesterase inhibitor Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level and ...

Uses

It is used as an ocular antihypertensive in the treatment of chronic

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye re ...

and, in some cases, accommodative

esotropia Esotropia is a form of strabismus in which one or both eyes turns inward. The condition can be constantly present, or occur intermittently, and can give the affected individual a "cross-eyed" appearance. It is the opposite of exotropia and usua ...

. It is available under several trade names such as Phospholine Iodide ( Wyeth-Ayerst). Echothiophate binds irreversibly to

cholinesterase The enzyme cholinesterase (EC 3.1.1.8, choline esterase; systematic name acylcholine acylhydrolase) catalyses the hydrolysis of choline-based esters: : an acylcholine + H2O = choline + a carboxylate Several of these serve as neurotransmitters ...

. Because of the very slow rate at which echothiophate is hydrolyzed by cholinesterase, its effects can last a week or more.

Adverse effect An adverse effect is an undesired harmful effect resulting from a Pharmaceutical drug, medication or other Surgery#Definitions, intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main ...

s include

muscle spasm A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder. A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscl ...

and other

systemic effect An adverse drug reaction (ADR) is a harmful, unintended result caused by taking medication. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs. The meaning of this term ...

Mechanism of action

It covalently binds by its phosphate group to serine group at the active site of the

. 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 Iodomethane, also called methyl iodide, and commonly abbreviated "MeI", is the chemical compound with the formula CH3I. It is a dense, colorless, volatile liquid. In terms of chemical structure, it is related to methane by replacement of one ...

, forming echothiophate.H.M. Fitch, (1959) : Echothiophate synthesis

References

{{Acetylcholine metabolism and transport modulators Acetylcholinesterase inhibitors Organothiophosphate esters Ophthalmology drugs Iodides Phosphorylthiocholines