Lodoxamide

Identification

Name
Lodoxamide
Accession Number
DB06794
Type
Small Molecule
Groups
Approved
Description

Lodoxamide is a mast-cell stabilizer for topical administration into the eye. Mast-cell stabilizers, first one approved being cromolyn sodium, are used in treatment of ocular hypersensitivity reactions such as vernal conjunctivitis. These conditions often require treatment with anti-inflammatory medications such as ophthalmic NSAIDs or topical steroids which may cause systemic or toxic effects long-term. Although less effective than topical steroids at decreasing inflammation, mast-cell stabilizers offer another treatment option and exhibit minimal adverse effects. Lodoxamide is marketed under the brand name Alomide by Alcon.

Structure
Thumb
Synonyms
  • N,N'-(2-chloro-5-cyano-m-phenylene)dioxamate
External IDs
U-42585E
Product Ingredients
IngredientUNIICASInChI Key
Lodoxamide tromethamine50LV9A548L63610-09-3JJOFNSLZHKIJEV-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AlomideSolution0.1 %OphthalmicNovartis1992-12-31Not applicableCanada
AlomideSolution / drops1 mg/mLOphthalmicAlcon, Inc.1993-09-30Not applicableUs
Categories
UNII
SPU695OD73
CAS number
53882-12-5
Weight
Average: 311.63
Monoisotopic: 310.9945126
Chemical Formula
C11H6ClN3O6
InChI Key
RVGLGHVJXCETIO-UHFFFAOYSA-N
InChI
InChI=1S/C11H6ClN3O6/c12-7-5(14-8(16)10(18)19)1-4(3-13)2-6(7)15-9(17)11(20)21/h1-2H,(H,14,16)(H,15,17)(H,18,19)(H,20,21)
IUPAC Name
{[3-(carboxyformamido)-2-chloro-5-cyanophenyl]carbamoyl}formic acid
SMILES
OC(=O)C(=O)NC1=CC(=CC(NC(=O)C(O)=O)=C1Cl)C#N

Pharmacology

Indication

Indicated in the treatment of the ocular disorders referred to by the terms vernal keratoconjunctivitis, vernal conjunctivitis, and vernal keratitis.

Structured Indications
Pharmacodynamics

Lodoxamide is a mast cell stabilizer that inhibits the in vivo Type 1 immediate hypersensitivity reaction. Lodoxamide therapy inhibits the increases in cutaneous vascular permeability that are associated with reagin or IgE and antigen-mediated reactions.

Mechanism of action

Although lodoxamide's precise mechanism of action is unknown, it is postulated that it prevents calcium influx into mast cells upon antigen stimulation and therefore stabilizes the membrane. By stabilizing the mast cell membrane from degranulation, lodoxamide consequently inhibits the release of intracellular histamine and other chemoattractant factors that primarily cause ocular symptoms. Lodoxamide's mechanism of action may be similar to cromolyn sodium, as both exhibit cross-tachyphylaxis.

Absorption

In a study of twelve healthy adult volunteers, topical administration of lodoxamide tromethamine ophthalmic solution 0.1%, one drop in each eye four times per day for ten days, did not result in any measurable lodoxamide plasma levels at a detection limit of 2.5 ng/mL.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Urinary excretion is the major route of elimination.

Half life

Elimination half-life was 8.5 hours in urine.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Lodoxamide.Experimental, Illicit
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Lodoxamide.Experimental
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Lodoxamide.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Lodoxamide.Experimental, Illicit
AmphetamineAmphetamine may decrease the sedative activities of Lodoxamide.Approved, Illicit, Investigational
BenzphetamineBenzphetamine may decrease the sedative activities of Lodoxamide.Approved, Illicit
Benzylpenicilloyl PolylysineLodoxamide may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Lodoxamide.Approved, Investigational
ChlorphentermineChlorphentermine may decrease the sedative activities of Lodoxamide.Illicit, Withdrawn
DextroamphetamineDextroamphetamine may decrease the sedative activities of Lodoxamide.Approved, Illicit
DiethylpropionDiethylpropion may decrease the sedative activities of Lodoxamide.Approved, Illicit
GepefrineGepefrine may decrease the sedative activities of Lodoxamide.Experimental
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Lodoxamide.Approved, Investigational
HydroxyamphetamineHydroxyamphetamine may decrease the sedative activities of Lodoxamide.Approved
Iofetamine I-123Iofetamine I-123 may decrease the sedative activities of Lodoxamide.Approved
LisdexamfetamineLisdexamfetamine may decrease the sedative activities of Lodoxamide.Approved, Investigational
MephedroneMephedrone may decrease the sedative activities of Lodoxamide.Investigational
MephentermineMephentermine may decrease the sedative activities of Lodoxamide.Approved
MethamphetamineMethamphetamine may decrease the sedative activities of Lodoxamide.Approved, Illicit
MethoxyphenamineMethoxyphenamine may decrease the sedative activities of Lodoxamide.Experimental
MidomafetamineMidomafetamine may decrease the sedative activities of Lodoxamide.Experimental, Illicit, Investigational
MMDAMMDA may decrease the sedative activities of Lodoxamide.Experimental, Illicit
PhenterminePhentermine may decrease the sedative activities of Lodoxamide.Approved, Illicit
PseudoephedrinePseudoephedrine may decrease the sedative activities of Lodoxamide.Approved
RitobegronRitobegron may decrease the sedative activities of Lodoxamide.Investigational
Food Interactions
No interactions found.

References

General References
  1. Avunduk AM, Avunduk MC, Kapicioglu Z, Akyol N, Tavli L: Mechanisms and comparison of anti-allergic efficacy of topical lodoxamide and cromolyn sodium treatment in vernal keratoconjunctivitis. Ophthalmology. 2000 Jul;107(7):1333-7. [PubMed:10890862]
  2. Lee S, Allard TR: Lodoxamide in vernal keratoconjunctivitis. Ann Pharmacother. 1996 May;30(5):535-7. [PubMed:8740338]
  3. Das D, Khan M, Gul A, Alam R: Safety and efficacy of lodoxamide in vernal keratoconjunctivitis. J Pak Med Assoc. 2011 Mar;61(3):239-41. [PubMed:21465936]
External Links
KEGG Drug
D04762
PubChem Compound
44564
PubChem Substance
310264890
ChemSpider
40543
ChEBI
135333
ChEMBL
CHEMBL1201266
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Lodoxamide
ATC Codes
S01GX05 — Lodoxamide
AHFS Codes
  • 52:02.00 — Antiallergic Agents
FDA label
Download (95.1 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionOphthalmic0.1 %
Solution / dropsOphthalmic1 mg/mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0361 mg/mLALOGPS
logP0.72ALOGPS
logP0.83ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)-6.7ChemAxon
pKa (Strongest Basic)0.73ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area156.59 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity69.9 m3·mol-1ChemAxon
Polarizability26.52 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

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

Taxonomy

Description
This compound belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acids and derivatives
Alternative Parents
Anilides / N-arylamides / Benzonitriles / Chlorobenzenes / Dicarboxylic acids and derivatives / Aryl chlorides / Secondary carboxylic acid amides / Nitriles / Carboxylic acids / Organopnictogen compounds
show 4 more
Substituents
Alpha-amino acid or derivatives / Anilide / Benzonitrile / N-arylamide / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Benzenoid
show 17 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Drug created on September 14, 2010 10:21 / Updated on May 22, 2018 23:54