Pemirolast

Identification

Name
Pemirolast
Accession Number
DB00885  (APRD00394)
Type
Small Molecule
Groups
Approved, Investigational
Description

Pemirolast potassium is a slightly yellow powder that is soluble in water. It is a mast cell stabilizer that acts as an antiallergic agent. As an ophthalmic aqueous sterile solution, pemirolast is used for the prevention of itching of the eyes caused by allergies such as hay fever, and allergic conjunctivitis. Pemirolast is potentially useful for prophylaxis of pulmonary hypersensitivity reactions to drugs such as paclitaxel.

Structure
Thumb
Synonyms
  • Pemirolast
  • Pemirolastum
  • Pemirox
External IDs
BMY 26517 / DE 068 / TBX
Product Ingredients
IngredientUNIICASInChI Key
Pemirolast potassium497A17OUUE100299-08-9NMMVKSMGBDRONO-UHFFFAOYSA-N
International/Other Brands
Alamast (Santen Pharmaceutical Co.) / Alegysal (Santen Pharmaceutical Co.)
Categories
UNII
2C09NV773M
CAS number
69372-19-6
Weight
Average: 228.2101
Monoisotopic: 228.075958908
Chemical Formula
C10H8N6O
InChI Key
HIANJWSAHKJQTH-UHFFFAOYSA-N
InChI
InChI=1S/C10H8N6O/c1-6-3-2-4-16-9(6)11-5-7(10(16)17)8-12-14-15-13-8/h2-5H,1H3,(H,12,13,14,15)
IUPAC Name
9-methyl-3-(2H-1,2,3,4-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one
SMILES
CC1=CC=CN2C(=O)C(=CN=C12)C1=NNN=N1

Pharmacology

Indication

For the prevention of itching of the eyes caused by allergies such as hay fever, and allergic conjunctivitis

Pharmacodynamics

Pemirolast is used for the prophylactic treatment of itching of the eye associated with allergic conjunctivitis. Pemirolast potassium is a mast cell stabilizer that inhibits the in vivo Type I immediate hypersensitivity reaction. Pemirolast inhibits the antigen-induced release of inflammatory mediators (e.g., histamine, leukotriene C4, D4, E4) from human mast cells. Allergic reactions lead to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis and vasodilatation (allowing blood fluids to enter the area to cause swelling). Pemirolast is a histamine H1 antagonist. It competes with histamine for the normal H1-receptor sites on effector cells of blood vessels to provide effective, temporary relief of watery and itchy eyes.

Mechanism of action

Pemirolast binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. Pemirolast has also been observed to inhibit antigen-stimulated calcium ion influx into mast cells through the blockage of calcium channels. Pemirolast inhibits the chemotaxis of eosinophils into ocular tissue, and prevents inflammatory mediator release from human eosinophils.

Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic (Ophthalmic)

Route of elimination

Following topical administration, about 10-15% of the dose was excreted unchanged in the urine.

Half life

4.5 hours (Ophthalmic)

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 Pemirolast.Experimental, Illicit
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Pemirolast.Experimental
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Pemirolast.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Pemirolast.Experimental, Illicit
AmphetamineAmphetamine may decrease the sedative activities of Pemirolast.Approved, Illicit, Investigational
BenzphetamineBenzphetamine may decrease the sedative activities of Pemirolast.Approved, Illicit
Benzylpenicilloyl PolylysinePemirolast may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Pemirolast.Approved, Investigational
ChlorphentermineChlorphentermine may decrease the sedative activities of Pemirolast.Illicit, Withdrawn
DextroamphetamineDextroamphetamine may decrease the sedative activities of Pemirolast.Approved, Illicit
DiethylpropionDiethylpropion may decrease the sedative activities of Pemirolast.Approved, Illicit
GepefrineGepefrine may decrease the sedative activities of Pemirolast.Experimental
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Pemirolast.Approved, Investigational
HydroxyamphetamineHydroxyamphetamine may decrease the sedative activities of Pemirolast.Approved
Iofetamine I-123Iofetamine I-123 may decrease the sedative activities of Pemirolast.Approved
LisdexamfetamineLisdexamfetamine may decrease the sedative activities of Pemirolast.Approved, Investigational
MephedroneMephedrone may decrease the sedative activities of Pemirolast.Investigational
MephentermineMephentermine may decrease the sedative activities of Pemirolast.Approved
MethamphetamineMethamphetamine may decrease the sedative activities of Pemirolast.Approved, Illicit
MethoxyphenamineMethoxyphenamine may decrease the sedative activities of Pemirolast.Experimental
MidomafetamineMidomafetamine may decrease the sedative activities of Pemirolast.Experimental, Illicit, Investigational
MMDAMMDA may decrease the sedative activities of Pemirolast.Experimental, Illicit
PhenterminePhentermine may decrease the sedative activities of Pemirolast.Approved, Illicit
PseudoephedrinePseudoephedrine may decrease the sedative activities of Pemirolast.Approved
RitobegronRitobegron may decrease the sedative activities of Pemirolast.Investigational
Food Interactions
Not Available

References

Synthesis Reference

Graziano Castaldi, "Process for the preparation of high purity pemirolast." U.S. Patent US20030032805, issued February 13, 2003.

US20030032805
General References
  1. Tinkelman DG, Berkowitz RB: A pilot study of pemirolast in patients with seasonal allergic rhinitis. Ann Allergy. 1991 Feb;66(2):162-5. [PubMed:1994787]
External Links
Human Metabolome Database
HMDB0015023
KEGG Drug
D01088
PubChem Compound
57697
PubChem Substance
46509034
ChemSpider
51990
ChEBI
134936
ChEMBL
CHEMBL1201198
Therapeutic Targets Database
DAP001064
PharmGKB
PA164781018
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pemirolast
FDA label
Download (372 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1

Pharmacoeconomics

Manufacturers
  • Santen inc
Packagers
  • Santen Inc.
  • Vistakon Pharmaceuticals LLC
Dosage forms
Not Available
Prices
Unit descriptionCostUnit
Alamast 0.1% drops11.39USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5034230No1994-07-022011-07-02Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP0Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.462 mg/mLALOGPS
logP0.13ALOGPS
logP1.46ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)5.8ChemAxon
pKa (Strongest Basic)-1.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area87.13 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity63.35 m3·mol-1ChemAxon
Polarizability21.96 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9766
Caco-2 permeable+0.6032
P-glycoprotein substrateNon-substrate0.6874
P-glycoprotein inhibitor INon-inhibitor0.7029
P-glycoprotein inhibitor IINon-inhibitor0.9336
Renal organic cation transporterNon-inhibitor0.8165
CYP450 2C9 substrateNon-substrate0.7256
CYP450 2D6 substrateNon-substrate0.8314
CYP450 3A4 substrateSubstrate0.5485
CYP450 1A2 substrateInhibitor0.874
CYP450 2C9 inhibitorNon-inhibitor0.8783
CYP450 2D6 inhibitorNon-inhibitor0.8729
CYP450 2C19 inhibitorNon-inhibitor0.8134
CYP450 3A4 inhibitorNon-inhibitor0.543
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5112
Ames testAMES toxic0.5453
CarcinogenicityNon-carcinogens0.8916
BiodegradationNot ready biodegradable0.9965
Rat acute toxicity2.3619 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9391
hERG inhibition (predictor II)Non-inhibitor0.8932
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
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 pyridopyrimidines. These are compounds containing a pyridopyrimidine, which consists of a pyridine fused to a pyrimidine. Pyridine is 6-membered ring consisting of five carbon atoms and a nitrogen atom. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridopyrimidines
Sub Class
Not Available
Direct Parent
Pyridopyrimidines
Alternative Parents
Pyrimidones / Methylpyridines / Tetrazoles / Heteroaromatic compounds / Lactams / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organic oxides
show 1 more
Substituents
Pyridopyrimidine / Pyrimidone / Methylpyridine / Pyridine / Pyrimidine / Azole / Tetrazole / Heteroaromatic compound / Lactam / Azacycle
show 8 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Drug created on June 13, 2005 07:24 / Updated on June 02, 2018 09:32