Echothiophate

Identification

Summary

Echothiophate is an acetylcholinesterase inhibitor used in ophthalmic preparations to increase the drainage of intraocular fluid; most commonly used for the treatment of glaucoma.

Brand Names
Phospholine Iodide
Generic Name
Echothiophate
DrugBank Accession Number
DB01057
Background

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

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 256.323
Monoisotopic: 256.113625809
Chemical Formula
C9H23NO3PS
Synonyms
  • 2-(Diethoxyphosphorylsulfanyl)ethyl-N,N,N-trimethylazanium iodide
  • Echothiophate
  • Ecothiopate
  • Ecothiopatum
  • Phospholine
External IDs
  • MI 217

Pharmacology

Indication

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

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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.

TargetActionsOrganism
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

Adverse Effects
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Toxicity

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

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
DipyridamoleThe therapeutic efficacy of Echothiophate can be decreased when used in combination with Dipyridamole.
FluoxetineThe risk or severity of QTc prolongation can be increased when Fluoxetine is combined with Echothiophate.
HaloperidolThe risk or severity of QTc prolongation can be increased when Echothiophate is combined with Haloperidol.
HydroxyzineThe risk or severity of QTc prolongation can be increased when Echothiophate is combined with Hydroxyzine.
LefamulinLefamulin may increase the QTc-prolonging activities of Echothiophate.
PitolisantEchothiophate may increase the QTc-prolonging activities of Pitolisant.
PonesimodThe risk or severity of bradycardia can be increased when Ponesimod is combined with Echothiophate.
TrazodoneThe risk or severity of QTc prolongation can be increased when Trazodone is combined with Echothiophate.
ZiprasidoneThe risk or severity of QTc prolongation can be increased when Echothiophate is combined with Ziprasidone.
Interactions
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Echothiophate iodideBA9QH3P00T513-10-0OVXQHPWHMXOFRD-UHFFFAOYSA-M
International/Other Brands
Echodide (Alcon)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Phospholine IodideSolution12.5 mg/5mLOphthalmicWyeth Pharmaceuticals Inc.2006-11-032006-11-03US flag
Phospholine IodidePowder, for solution6.25 mg/5mLOphthalmicCangene bioPharma Inc2005-12-012010-02-25US flag
Phospholine IodideSolution3 mg/5mLOphthalmicWyeth Pharmaceuticals Inc.2006-11-032006-11-03US flag
Phospholine IodidePowder, for solution6.25 mg/5mLOphthalmicCangene bioPharma Inc2005-12-012010-02-25US flag
Phospholine IodideSolution1.5 mg/5mLOphthalmicWyeth Pharmaceuticals Inc.2006-11-032006-11-03US flag
Phospholine Iodide - Liq Pws 3mg/5mlLiquid; Powder, for solution3 mg / 5 mLOphthalmicStorz, Division Of Wyeth Ayerst Canada Inc.1997-04-291999-08-12Canada flag
Phospholine Iodide - Pws 12.5mg/5mlPowder, for solution12.5 mg / 5 mLOphthalmicStorz, Division Of Wyeth Ayerst Canada Inc.1997-08-291999-08-12Canada flag
Phospholine Iodide - Pws 6.25mg/5mlPowder, for solution6.25 mg / 5 mLOphthalmicStorz, Division Of Wyeth Ayerst Canada Inc.1997-04-292000-08-02Canada flag
Phospholine Iodide 12.5mg/5mlPowder, for solution12.5 mg / 5 mLOphthalmicWyeth Ayerst Canada Inc.1994-12-312001-08-30Canada flag
Phospholine Iodide 3mg/5mlPowder, for solution3 mg / 5 mLOphthalmicWyeth Ayerst Canada Inc.1998-12-022001-05-07Canada flag

Categories

ATC Codes
S01EB03 — Ecothiopate
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Aliphatic acyclic compound / Amine / Hydrocarbon derivative / Organic cation / Organic oxide / Organic oxygen compound / Organic salt / Organooxygen compound / Organopnictogen compound / Organosulfur compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
quaternary ammonium ion, phosphocholines, organic thiophosphate (CHEBI:4753)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
0F350BVT6S
CAS number
6736-03-4
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

References

Synthesis Reference

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

General References
  1. Reddy RH: Echothiophate iodide: its use in accommodative esotropia (high Ac/A ratio). Indian J Ophthalmol. 1982 Jul;30(4):225. [Article]
  2. 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. [Article]
Human Metabolome Database
HMDB0015190
KEGG Drug
D02193
KEGG Compound
C06975
PubChem Compound
10548
PubChem Substance
46505944
ChemSpider
10108
RxNav
89778
ChEBI
4753
ChEMBL
CHEMBL1201341
ZINC
ZINC000001530628
Therapeutic Targets Database
DAP000962
PharmGKB
PA164743139
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Echothiophate
FDA label
Download (45 KB)
MSDS
Download (87.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Unknown StatusPreventionMyopia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Wyeth Pharmaceuticals
Dosage Forms
FormRouteStrength
Powder, for solutionOphthalmic6.25 mg/5mL
SolutionOphthalmic1.5 mg/5mL
SolutionOphthalmic12.5 mg/5mL
SolutionOphthalmic3 mg/5mL
Liquid; powder, for solutionOphthalmic3 mg / 5 mL
Powder, for solutionOphthalmic12.5 mg / 5 mL
Powder, for solutionOphthalmic3 mg / 5 mL
Powder, for solutionOphthalmic6.25 mg / 5 mL
Prices
Unit descriptionCostUnit
Phospholine iodide 0.125%16.09USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US2911430No1958-01-151978-01-15US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)124-124.5Fitch, H.M.; U.S. Patent 2,911,430; November 3, 1959; assigned to Campbell Pharmaceuticals, Inc.
water solubilitySolubleNot Available
logP-2.25Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.297 mg/mLALOGPS
logP-2.2ALOGPS
logP-3.1ChemAxon
logS-3ALOGPS
pKa (Strongest Basic)-8.2ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area35.53 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity78.14 m3·mol-1ChemAxon
Polarizability27.65 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.7708
Blood Brain Barrier+0.91
Caco-2 permeable+0.5098
P-glycoprotein substrateNon-substrate0.6063
P-glycoprotein inhibitor INon-inhibitor0.8482
P-glycoprotein inhibitor IINon-inhibitor0.962
Renal organic cation transporterNon-inhibitor0.7835
CYP450 2C9 substrateNon-substrate0.8237
CYP450 2D6 substrateNon-substrate0.7603
CYP450 3A4 substrateNon-substrate0.5252
CYP450 1A2 substrateNon-inhibitor0.8317
CYP450 2C9 inhibitorNon-inhibitor0.7972
CYP450 2D6 inhibitorNon-inhibitor0.8991
CYP450 2C19 inhibitorNon-inhibitor0.8013
CYP450 3A4 inhibitorNon-inhibitor0.9093
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9377
Ames testNon AMES toxic0.8524
CarcinogenicityCarcinogens 0.7021
BiodegradationReady biodegradable0.9528
Rat acute toxicity4.3595 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5816
hERG inhibition (predictor II)Non-inhibitor0.7263
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets
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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
  1. 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. [Article]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Carriers

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
  1. 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. [Article]

Drug created on June 13, 2005 13:24 / Updated on May 07, 2021 21:33