PEMIROLAST

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H8N6O
Molecular Weight	228.2101
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC=CN2C(=O)C(=CN=C12)C3=NN=NN3

InChI

InChIKey=HIANJWSAHKJQTH-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.mimaki-family-japan.com/item/detail?item_prefix=TF&item_code=001446&item_branch=001 | http://adisinsight.springer.com/drugs/800013853 | https://www.drugs.com/monograph/pemirolast-potassium.html

Pemirolast is a mast cell stabilizer that acts as an antiallergic agent, it is approved in Japan for the treatment of bronchial asthma and of allergic rhinitis. Pemirolast strongly inhibits extracellular Ca2+ influx and the release of intracellular Ca2+, an important factor in the release of chemical mediators, by inhibiting inositol-phospholipid metabolism in mast cells. It also inhibits the release of arachidonic acid. Furthermore contribution of increasing effect on c-AMP based on inhibiting phosphodiesterase is suggested. Main pharmacological effects is an inhibition of release of chemical mediators, e.g. histamine, LTB4, LTC4, LTD4, PGD2, TXB2 and PAF from human lung tissues, abraded fragments of the nasal mucosa, and peripheral leukocytes, rat peritoneal exudate cells, and rat and guniea pig lung tissues.

CNS Activity

Approval Year

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergic rhinitis 100 Sources: http://adisinsight.springer.com/drugs/800013853	Primary		Approved 8429	Alegysal Approved Use Unknown
Bronchial asthma 50 Sources: https://www.mimaki-family-japan.com/item/detail?item_prefix=TF&item_code=001446&item_branch=001	Primary		Approved 8429	Alegysal Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
0.283 μg/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/21079_Alamast.pdf	0.2 mg/kg single, oral dose: 0.2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		PEMIROLAST plasma	Canis lupus population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
4.7 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21079lbl.pdf	2 drop 4 times / day steady-state, ocular dose: 2 drop route of administration: Ocular experiment type: STEADY-STATE co-administered:		PEMIROLAST plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
0.315 μg × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/21079_Alamast.pdf	0.2 mg/kg single, oral dose: 0.2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		PEMIROLAST plasma	Canis lupus population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21079lbl.pdf	2 drop 4 times / day steady-state, ocular dose: 2 drop route of administration: Ocular experiment type: STEADY-STATE co-administered:		PEMIROLAST plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
34% OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/21079_Alamast.pdf	0.2 mg/kg single, oral dose: 0.2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		PEMIROLAST plasma	Canis lupus population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

Doses

Dose	Population	Adverse events
0.1 % 2 times / day steady, ophthalmic Recommended Dose: 0.1 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.1 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12772816/	unhealthy, adult n = 39 Health Status: unhealthy Condition: allergic conjunctivitis Age Group: adult Sex: M+F Population Size: 39 Sources: https://pubmed.ncbi.nlm.nih.gov/12772816/	Disc. AE: Eye allergy... AEs leading to discontinuation/dose reduction: Eye allergy (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/12772816/

AEs

AE	Significance	Dose	Population
Eye allergy	1 patient Disc. AE	0.1 % 2 times / day steady, ophthalmic Recommended Dose: 0.1 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.1 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12772816/	unhealthy, adult n = 39 Health Status: unhealthy Condition: allergic conjunctivitis Age Group: adult Sex: M+F Population Size: 39 Sources: https://pubmed.ncbi.nlm.nih.gov/12772816/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16498570/ Page: 7.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://patents.google.com/patent/US9415051

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-1114	http://www.3bsc.com/index/pro_info.php?id=54830
AHH Chemical co.,ltd	MT-57697	http://www.ahhchemical.com/product/MT-57697.html
AK Scientific, Inc. (AKSCI)	K155	http://www.aksci.com/item_detail.php?cat=K155
Achemtek	0101-001592	http://www.achemtek.com/69372-19-6
Ambinter	Amb22167568	http://www.ambinter.com/reference/22167568
Aurora Fine Chemicals LLC	A17.893.011	http://online.aurorafinechemicals.com/info?ID=A17.893.011
BioChemPartner	BCP21140	http://www.biochempartner.com/69372-19-6-BCP21140
Debye Scientific	DB-055262	http://www.debyesci.com/cas_69372-19-6.html
Finetech	FT-0630784	http://www.finetechnology-ind.com/prod/detail/pub/69372-19-6.html
Glentham Life Sciences	GP6235	http://www.glentham.com/products/product/GP6235/
Hairui	HR142155	http://www.hairuichem.com/en/product/69372-19-6.html
Smolecule	S583672	https://www.smolecule.com/products/s583672
Synblock Inc	SB18791	http://www.synblock.com/product/69372-19-6.html
THE BioTek	bt-459038	https://www.thebiotek.com/product/others/bt-459038
Yuhao Chemical	YH65147	http://www.chemyuhao.com/69372-19-6 .html
eNovation Chemicals	D510198	https://www.enovationchem.com/ProductDetails.asp?ProductID=D510198
iChemical	EBD545840	http://www.ichemical.com/products/69372-19-6.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
A pilot study of pemirolast in patients with seasonal allergic rhinitis.	1991 Feb	1994787
Effects of topical anti-inflammatory and antiallergic eyedrops on prostaglandin E2-induced aqueous flare elevation in pigmented rabbits.	2002 Jul	12096966
Pemirolast potassium 0.1% ophthalmic solution is an effective treatment for allergic conjunctivitis: a pooled analysis of two prospective, randomized, double-masked, placebo-controlled, phase III studies.	2002 Oct	12419098
A combined analysis of two studies assessing the ocular comfort of antiallergy ophthalmic agents.	2003 Apr	12809959
Two mast cell stabilizers, pemirolast potassium 0.1% and nedocromil sodium 2%, in the treatment of seasonal allergic conjunctivitis: a comparative study.	2003 Jan-Feb	12772816
A comparative trial of the safety and efficacy of 0.1 percent pemirolast potassium ophthalmic solution dosed twice or four times a day in patients with seasonal allergic conjunctivitis.	2004 Apr	15117570
Comparison of 0.1% bromfenac sodium and 0.1% pemirolast potassium for the treatment of allergic conjunctivitis.	2004 Nov-Dec	15592786
Acute asthma attack caused by ophthalmic application of antiallergic agents.	2004 Sep-Oct	15486771
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Increasing effect by simultaneous use of levocabastine and pemirolast on experimental allergic conjunctivitis in rats.	2005 Mar	15744071
Comparison of antigen-induced leukotriene and histamine release from nasal scrapings in allergic rhinitis.	2005 Sep	16218513
Peripheral interstitial keratitis: a novel manifestation of ocular mastocytosis.	2006 Apr	16633043
Tetrazole compounds: the effect of structure and pH on Caco-2 cell permeability.	2006 Apr	16498570
A late cutaneous response in actively sensitized rats: a new method for evaluating the efficacy of antiallergic drugs.	2006 Aug	16891762
A comparative study on the cost of new antibiotics and drugs of other therapeutic categories.	2006 Dec 20	17183637
Prophylactic effect of pemirolast, an antiallergic agent, against hypersensitivity reactions to paclitaxel in patients with ovarian cancer.	2006 May 15	16353140
The effect of a combined therapy with a histamine H1 antagonist and a chemical mediator release inhibitor on allergic conjunctivitis.	2008	18463425
Suppressive activity of pemirolast potassium, an antiallergic drug, on glomerulonephritis. Studies in glomerulonephritis model rats and in patients with chronic glomerulonephritis concurrently affected by allergic rhinitis.	2008	18368946
Treatment of allergic conjunctivitis with olopatadine hydrochloride eye drops.	2008 Sep	19668750
Involvement of substance P in peripheral neuropathy induced by paclitaxel but not oxaliplatin.	2011 Apr	21233199

Patents

Sample Use Guides

In Vivo Use Guide

reatment with pemirolast 200 mg bid for 14-16 days

Route of Administration: Oral

In Vitro Use Guide

It was investigated the effect of pemirolast on the release of leukotriene C4 (LTC4) and eosinophil cationic protein (ECP) from human eosinophils. Pemirolast (10(-6) to 10(-3) M) inhibited A23187-induced LTC4 release from the eosinophils in a dose-dependent fashion with 77% inhibition at 10(-3) M. Pemirolast (10(-5) to 10(-3) M) inhibited A23187-induced ECP release from the eosinophils in a dose-dependent fashion with 42% inhibition at 10(-3) M. Pemirolast (10(-4) and 10(-3) M) also inhibited PAF-induced and FMLP-induced ECP release from the eosinophils. It was concluded that pemirolast prevented the activation of human eosinophils to inhibit LTC4 and ECP release.

Name

Type

Language

PEMIROLAST

Official Name

English

PERMIROLAST [VANDF]

Common Name

English

pemirolast [INN]

Common Name

English

9-METHYL-3-(1H-TETRAZOL-5-YL)-4H-PYRIDO(1,2-A)PYRIMIDIN-4-ONE

Systematic Name

English

Pemirolast [WHO-DD]

Common Name

English

PEMIROLAST [VANDF]

Common Name

English

PEMIROLAST [HSDB]

Common Name

English

PEMIROLAST [MI]

Common Name

English

PEMIROX

Brand Name

English

4H-PYRIDO(1,2-A)PYRIMIDIN-4-ONE, 9-METHYL-3-(1H-TETRAZOL-5-YL)-

Systematic Name

English

Classification Tree Code System Code

NDF-RT

N0000175630