A potent, long-acting irreversible cholinesterase inhibitor used as an ocular hypertensive in the treatment of glaucoma. Occasionally used for accomodative esotropia.

Structure

Similar Structures

Synonyms

2-(Diethoxyphosphorylsulfanyl)ethyl-N,N,N-trimethylazanium iodide
Echothiophate
Ecothiopate
Ecothiopatum
Phospholine

External IDs

MI 217

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Echothiophate iodide	BA9QH3P00T	513-10-0	OVXQHPWHMXOFRD-UHFFFAOYSA-M

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Phospholine Iodide	Solution	1.5 mg/5mL	Ophthalmic	Wyeth Pharmaceuticals Inc.	2006-11-03	2006-11-03
Phospholine Iodide	Powder, for solution	6.25 mg/5mL	Ophthalmic	Cangene bioPharma Inc	2005-12-01	2010-02-25
Phospholine Iodide	Powder, for solution	6.25 mg/5mL	Ophthalmic	Cangene bioPharma Inc	2005-12-01	2010-02-25
Phospholine Iodide	Solution	12.5 mg/5mL	Ophthalmic	Wyeth Pharmaceuticals Inc.	2006-11-03	2006-11-03
Phospholine Iodide	Solution	3 mg/5mL	Ophthalmic	Wyeth Pharmaceuticals Inc.	2006-11-03	2006-11-03
Phospholine Iodide - Liq Pws 3mg/5ml	Liquid; Powder, for solution	3 mg	Ophthalmic	Storz, Division Of Wyeth Ayerst Canada Inc.	1997-04-29	1999-08-12
Phospholine Iodide - Pws 12.5mg/5ml	Powder, for solution	12.5 mg	Ophthalmic	Storz, Division Of Wyeth Ayerst Canada Inc.	1997-08-29	1999-08-12
Phospholine Iodide - Pws 6.25mg/5ml	Powder, for solution	6.25 mg	Ophthalmic	Storz, Division Of Wyeth Ayerst Canada Inc.	1997-04-29	2000-08-02
Phospholine Iodide 12.5mg/5ml	Powder, for solution	12.5 mg	Ophthalmic	Wyeth Ayerst Canada Inc.	1994-12-31	2001-08-30
Phospholine Iodide 3mg/5ml	Powder, for solution	3 mg	Ophthalmic	Wyeth Ayerst Canada Inc.	1998-12-02	2001-05-07

International/Other Brands

Echodide (Alcon)

Categories

UNII

0F350BVT6S

CAS number

6736-03-4

Weight

Average: 256.323
Monoisotopic: 256.113625809

Chemical Formula

C₉H₂₃NO₃PS

InChI Key

BJOLKYGKSZKIGU-UHFFFAOYSA-N

InChI

InChI=1S/C9H23NO3PS/c1-6-12-14(11,13-7-2)15-9-8-10(3,4)5/h6-9H2,1-5H3/q+1

IUPAC Name

diethyl {[2-(trimethylazaniumyl)ethyl]sulfanyl}phosphonate

SMILES

CCOP(=O)(OCC)SCC[N+](C)(C)C

Pharmacology

Indication

For use in the treatment of subacute or chronic angle-closure glaucoma after iridectomy or where surgery is refused or contraindicated.

Associated Conditions

Pharmacodynamics

Echothiophate Iodide is a potent, long-acting cholinesterase inhibitor used as a miotic in the treatment of glaucoma. Echothiophate iodide will depress both plasma and erythrocyte cholinesterase levels in most patients after a few weeks of eyedrop therapy.

Mechanism of action

Echothiophate Iodide is a long-acting cholinesterase inhibitor for topical use which enhances the effect of endogenously liberated acetylcholine in iris, ciliary muscle, and other parasympathetically innervated structures of the eye. Echothiophate iodide binds irreversibly to cholinesterase, and is long acting due to the slow rate of hydrolysis by cholinesterase. It causes miosis, increase in facility of outflow of aqueous humor, fall in intraocular pressure, and potentiation of accommodation.

Target	Actions	Organism
ACholinesterase	inhibitor	Humans

Absorption

This ophthalmic medication may be systemically absorbed.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half life

Not Available

Clearance

Not Available

Toxicity

Side effects include blurred vision or change in near or distant vision and eye pain. LD50: 174 mcg/kg in rats. (MSDS)

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
Succinylcholine	Echothiophate may increase the neuromuscular blocking activities of Succinylcholine.

Food Interactions

Not Available

References

Synthesis Reference

Fitch, H.M.; U.S. Patent 2,911,430; November 3, 1959; assigned to Campbell Pharmaceuticals, Inc.

General References

Reddy RH: Echothiophate iodide: its use in accommodative esotropia (high Ac/A ratio). Indian J Ophthalmol. 1982 Jul;30(4):225. [PubMed:7166393]
Schmidt KG, Horowitz Y, Buckman G, Segev E, Levinger E, Geyer O: Lowering of IOP by echothiophate iodide in pseudophakic eyes with glaucoma. Curr Eye Res. 2010 Aug;35(8):698-702. doi: 10.3109/02713681003794076. [PubMed:20673046]

External Links

Human Metabolome Database: HMDB0015190
KEGG Drug: D02193
KEGG Compound: C06975
PubChem Compound: 10548
PubChem Substance: 46505944
ChemSpider: 10108
ChEBI: 4753
ChEMBL: CHEMBL1201341
Therapeutic Targets Database: DAP000962
PharmGKB: PA164743139
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Echothiophate

ATC Codes

S01EB03 — Ecothiopate

FDA label

Download (45 KB)

MSDS

Download (87.9 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Not Yet Recruiting	Prevention	Myopia	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Wyeth Pharmaceuticals

Dosage forms

Form	Route	Strength
Powder, for solution	Ophthalmic	6.25 mg/5mL
Solution	Ophthalmic	1.5 mg/5mL
Solution	Ophthalmic	12.5 mg/5mL
Solution	Ophthalmic	3 mg/5mL
Liquid; powder, for solution	Ophthalmic	3 mg
Powder, for solution	Ophthalmic	12.5 mg
Powder, for solution	Ophthalmic	3 mg
Kit		6.25 mg/5mL
Powder, for solution	Ophthalmic	6.25 mg

Prices

Unit description	Cost	Unit
Phospholine iodide 0.125%	16.09USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US2911430	No	1958-01-15	1978-01-15

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	124-124.5	Fitch, H.M.; U.S. Patent 2,911,430; November 3, 1959; assigned to Campbell Pharmaceuticals, Inc.
water solubility	Soluble	Not Available
logP	-2.25	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.297 mg/mL	ALOGPS
logP	-2.2	ALOGPS
logP	-3.1	ChemAxon
logS	-3	ALOGPS
pKa (Strongest Basic)	-8.2	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	1	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	35.53 Å²	ChemAxon
Rotatable Bond Count	8	ChemAxon
Refractivity	78.14 m³·mol^-1	ChemAxon
Polarizability	27.65 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	-	0.7708
Blood Brain Barrier	+	0.91
Caco-2 permeable	+	0.5098
P-glycoprotein substrate	Non-substrate	0.6063
P-glycoprotein inhibitor I	Non-inhibitor	0.8482
P-glycoprotein inhibitor II	Non-inhibitor	0.962
Renal organic cation transporter	Non-inhibitor	0.7835
CYP450 2C9 substrate	Non-substrate	0.8237
CYP450 2D6 substrate	Non-substrate	0.7603
CYP450 3A4 substrate	Non-substrate	0.5252
CYP450 1A2 substrate	Non-inhibitor	0.8317
CYP450 2C9 inhibitor	Non-inhibitor	0.7972
CYP450 2D6 inhibitor	Non-inhibitor	0.8991
CYP450 2C19 inhibitor	Non-inhibitor	0.8013
CYP450 3A4 inhibitor	Non-inhibitor	0.9093
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9377
Ames test	Non AMES toxic	0.8524
Carcinogenicity	Carcinogens	0.7021
Biodegradation	Ready biodegradable	0.9528
Rat acute toxicity	4.3595 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.5816
hERG inhibition (predictor II)	Non-inhibitor	0.7263

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available

Taxonomy

Description: This compound belongs to the class of organic compounds known as tetraalkylammonium salts. These are organonitrogen compounds containing a quaternary ammonium substituted with four alkyl chains.
Kingdom: Organic compounds
Super Class: Organic nitrogen compounds
Class: Organonitrogen compounds
Sub Class: Quaternary ammonium salts
Direct Parent: Tetraalkylammonium salts
Alternative Parents: Sulfenyl compounds / Organothiophosphorus compounds / Organopnictogen compounds / Organooxygen compounds / Organic salts / Organic oxides / Hydrocarbon derivatives / Amines / Organic cations
Substituents: Tetraalkylammonium salt / Sulfenyl compound / Organothiophosphorus compound / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Organic salt / Organosulfur compound / Organooxygen compound
Molecular Framework: Aliphatic acyclic compounds
External Descriptors: quaternary ammonium ion, phosphocholines, organic thiophosphate (CHEBI:4753)

Targets

Details1. Cholinesterase

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Identical protein binding
Specific Function: Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name: BCHE
Uniprot ID: P06276
Uniprot Name: Cholinesterase
Molecular Weight: 68417.575 Da

References

Henderson EG, Post-Munson DJ, Reynolds LS, Epstein PM: Echothiophate and cogeners decrease the voltage dependence of end-plate current decay in frog skeletal muscle. J Pharmacol Exp Ther. 1989 Dec;251(3):810-6. [PubMed:2481033]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Carriers

Details1. Serum albumin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Toxic substance binding
Specific Function: Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name: ALB
Uniprot ID: P02768
Uniprot Name: Serum albumin
Molecular Weight: 69365.94 Da

References

Peeples ES, Schopfer LM, Duysen EG, Spaulding R, Voelker T, Thompson CM, Lockridge O: Albumin, a new biomarker of organophosphorus toxicant exposure, identified by mass spectrometry. Toxicol Sci. 2005 Feb;83(2):303-12. Epub 2004 Nov 3. [PubMed:15525694]

Drug created on June 13, 2005 07:24 / Updated on April 21, 2019 05:48

Echothiophate

Identification

Structure for Echothiophate (DB01057)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

Carriers

References