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Details

Stereochemistry ACHIRAL
Molecular Formula C19H15NO7.Ca
Molecular Weight 409.403
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NEDOCROMIL CALCIUM

SMILES

[Ca++].CCCC1=C2OC(=CC(=O)C2=CC3=C1N(CC)C(=CC3=O)C([O-])=O)C([O-])=O

InChI

InChIKey=FGUNXXYEYHFDNX-UHFFFAOYSA-L
InChI=1S/C19H17NO7.Ca/c1-3-5-9-16-10(13(21)7-12(18(23)24)20(16)4-2)6-11-14(22)8-15(19(25)26)27-17(9)11;/h6-8H,3-5H2,1-2H3,(H,23,24)(H,25,26);/q;+2/p-2

HIDE SMILES / InChI

Description

Nedocromil is a medication considered as mast cell stabilizer used to treat itching associated with allergic conjunctivitis. Nedocromil has been shown to inhibit the in vitro activation of, and mediator release from, a variety of inflammatory cell types associated with asthma, including eosinophils, neutrophils, macrophages, mast cells, monocytes, and platelets. Nedocromil inhibits activation and release of inflammatory mediators such as histamine, prostaglandin D2 and leukotrienes c4 from different types of cells in the lumen and mucosa of the bronchial tree. These mediators are derived from arachidonic acid metabolism through the lipoxygenase and cyclo-oxygenase pathways. The mechanism of action of nedocromil may be due partly to inhibition of axon reflexes and release of sensory neuropeptides, such as substance P, neurokinin A, and calcitonin-geneñrelated peptides. The result is inhibition of bradykinin-induced bronchoconstriction. Nedocromil does not possess any bronchodilator, antihistamine, or corticosteroid activity. Nedocromil is indicated for the treatment of itching associated with allergic conjunctivitis.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
TILADE
Primary
TILADE

Cmax

ValueDoseCo-administeredAnalytePopulation
13.7 ng/mL
6 μg/kg bw single, intravenous
NEDOCROMIL plasma
Homo sapiens
2.1 ng/mL
4 mg single, respiratory
NEDOCROMIL plasma
Homo sapiens
5.8 ng/mL
70.5 mg single, oral
NEDOCROMIL plasma
Homo sapiens
2.8 ng/mL
4 mg single, respiratory
NEDOCROMIL plasma
Homo sapiens
2.6 ng/mL
20 mg single, respiratory
NEDOCROMIL plasma
Homo sapiens
3.3 ng/mL
4 mg single, respiratory
NEDOCROMIL plasma
Homo sapiens
13.4 ng/mL
0.42 mg single, intravenous
NEDOCROMIL plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
10.4 ng × h/mL
6 μg/kg bw single, intravenous
NEDOCROMIL plasma
Homo sapiens
4.6 ng × h/mL
4 mg single, respiratory
NEDOCROMIL plasma
Homo sapiens
49.1 ng × h/mL
70.5 mg single, oral
NEDOCROMIL plasma
Homo sapiens
5.6 ng × h/mL
4 mg single, respiratory
NEDOCROMIL plasma
Homo sapiens
6.2 ng × h/mL
20 mg single, respiratory
NEDOCROMIL plasma
Homo sapiens
9.4 ng × h/mL
4 mg single, respiratory
NEDOCROMIL plasma
Homo sapiens
8.9 ng × h/mL
0.42 mg single, intravenous
NEDOCROMIL plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
21.1 h
70.5 mg single, oral
NEDOCROMIL plasma
Homo sapiens
1.5 h
4 mg single, respiratory
NEDOCROMIL plasma
Homo sapiens
2.3 h
4 mg single, respiratory
NEDOCROMIL plasma
Homo sapiens
31.6 h
0.42 mg single, intravenous
NEDOCROMIL plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
Instill 1-2 gtt in each eye twice daily throughout time of exposure (ie, until pollen season is over or offending allergen terminated)
Route of Administration: Topical
In Vitro Use Guide
Eosinophil chemotaxis was studied using a modified Boyden chamber technique. Sets of six chambers each were set up to investigate different experimental conditions. Half a millilitre of either medium 199, conditioned medium, or conditioned medium containing 10^-7, 10^-6 or 10^-5 M nedocromil sodium, was placed in the lower compartment of each chamber, and incubated for 90 min at 37°C in the presence of 2510^3 eosinophils in the upper compartment, separated by an 8 m pore size microporous polycarbonate membrane. At the end of incubation, the membrane was removed, fixed in absolute alcohol for 5 min and then washed under running tap water for 1 min. The membrane was stained with Chromotrope R for 5 min. The stained membrane was dehydrated in absolute alcohol for 5 min, cleared in CNP 30 reagent (BDH LaboratorySupplies, Lutterworth, UK), and then mounted in Styrolite™ mounting medium. The membrane was immediately examined by light microscopy, and the number of eosinophils coming through to the other side of the membrane was counted in 10 random high power fields (HPF) at x40 magnification.