DIMETHINDENE MALEATE

US Previously Marketed

First approved in 1960

Details

Stereochemistry	RACEMIC
Molecular Formula	C20H24N2.C4H4O4
Molecular Weight	408.4901
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.CC(C1=C(CCN(C)C)CC2=C1C=CC=C2)C3=CC=CC=N3

InChI

InChIKey=SWECWXGUJQLXJF-BTJKTKAUSA-N

InChI=1S/C20H24N2.C4H4O4/c1-15(19-10-6-7-12-21-19)20-17(11-13-22(2)3)14-16-8-4-5-9-18(16)20;5-3(6)1-2-4(7)8/h4-10,12,15H,11,13-14H2,1-3H3;1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

Description
Sources: https://www.drugbank.ca/drugs/DB08801

Dimetindene (trade name Fenistil; other name dimethindene maleate) is a potent antipruritic antihistamine, characterized by the small size of its effective dose and its rapidity of action. Dimetindene is an antihistamine/anticholinergic that is a selective H1 antagonist. Its effect sets in after 20 to 60 minutes and lasts several hours. Dimetindene drops as well as Dimetindene syrup is particularly indicated in pediatric practice. Dimetindene is indicated as symptomatic treatment of allergic reactions: urticaria, allergies of the upper respiratory tract such as hay fever and perennial rhinitis, food, and drug allergies; pruritus of various origins, except pruritus due to cholestasis; insect bites. Dimetindene is also indicated for pruritus in eruptive skin diseases such as chicken-pox. Dimetindene can be as an adjuvant in eczema and other pruriginous dermatoses of allergic origin.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H1 receptor 315 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12593665	Antagonist 2778		0.692 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Urticaria 39 Sources: http://pcm.me/fenistil-%C2%AE/	Primary	Approved 8429	Fenistil Approved Use Unknown
Respiratory allergies 2 Sources: http://pcm.me/fenistil-%C2%AE/	Primary	Approved 8429	Fenistil Approved Use Unknown
Dermatoses 23 Sources: http://pcm.me/fenistil-%C2%AE/	Primary	Approved 8429	Fenistil Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
14.6 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/2096106/	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		DIMETHINDENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
101.3 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/2096106/	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		DIMETHINDENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.41 h REVIEW https://pubmed.ncbi.nlm.nih.gov/2096106/	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		DIMETHINDENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.28 mg 2 times / day multiple, intranasal Recommended Dose: 0.28 mg, 2 times / day Route: intranasal Route: multiple Dose: 0.28 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14579656/	unhealthy, 18 -69 n = 76 Health Status: unhealthy Condition: seasonal allergic rhinitis Age Group: 18 -69 Sex: M+F Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/14579656/	Sources: https://pubmed.ncbi.nlm.nih.gov/14579656/
0.1 % 1 times / day single, topical Highest studied dose Dose: 0.1 %, 1 times / day Route: topical Route: single Dose: 0.1 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10337458/	healthy, 33 (21-54) n = 24 Health Status: healthy Age Group: 33 (21-54) Sex: M+F Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/10337458/	Sources: https://pubmed.ncbi.nlm.nih.gov/10337458/
6 mg 1 times / day single, oral Highest studied dose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1773908/	healthy, adult n = 60 Health Status: healthy Age Group: adult Sex: M Population Size: 60 Sources: https://pubmed.ncbi.nlm.nih.gov/1773908/	Sources: https://pubmed.ncbi.nlm.nih.gov/1773908/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587		inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19663387/	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19663387/	yes [IC50 32.5 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/19663387/

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY560685	https://www.001chemical.com/chem/5636-83-9
3B Scientific (Wuhan) Corp	3B2-1239	http://www.3bsc.com/index/pro_info.php?id=54955
AA Blocks	AA00EA7N	https://www.aablocks.com/goods/Goods/detail?id=AA00EA7N
AHH Chemical co.,ltd	MT-50230	http://www.ahhchemical.com/product/MT-50230.html
BLD Pharm	BD125253	http://www.bldpharm.com/products/5636-83-9.html
Clearsynth	CS-P-00945	https://www.clearsynth.com/en/CSP00945.html
Finetech	FT-0625024	http://www.finetechnology-ind.com/prod/detail/pub/5636-83-9.html
Hairui	HR100506	http://www.hairuichem.com/en/product/5636-83-9.html
Molcore	MC560685	https://www.molcore.com/product/5636-83-9
Smolecule	S526182	http://www.smolecule.com/products/s526182
THE BioTek	bt-265090	https://www.thebiotek.com/product/inhibitors/bt-265090
abcr GmbH	AB393645	http://www.abcr.com/shop/en/AB393645
eNovation Chemicals	D665175	https://www.enovationchem.com/ProductDetails.asp?ProductID=D665175

PubMed

Title	Date	PubMed
[Antimycobacterial antihistaminics].	1989 Aug	2513793
[Antipruritic effect of antihistaminic and local anesthetic topical agents after iontophoretic histamine stimulation].	1996 May	8707580
Influence of peak measurement parameters on the quality of chiral electrophoretic separations.	2003 Aug	12900858
Pruritic urticarial papules and plaques of pregnancy (PUPPP)--a case report.	2003 May-Jun	12891469
Influence of methanol on the enantioresolution of antihistamines with carboxymethyl-beta-cyclodextrin in capillary electrophoresis.	2004 Aug	15352017
Anaphylaxis to intravenous sinistrin.	2004 Dec	15536136
[Dimethindene determination in various dosage forms by means of capillary isotachophoresis].	2005 Sep	16209438
Anaphylactic shock caused by buffalo's mozzarella cheese.	2008 Jul	18683300
Analytical method for simultaneously measuring ex vivo drug receptor occupancy and dissociation rate: application to (R)-dimethindene occupancy of central histamine H1 receptors.	2009	19308787
Glioblastoma cells express functional cell membrane receptors activated by daily used medical drugs.	2009 Dec	19543745
Induction of anti-tumor immunity by trifunctional antibodies in patients with peritoneal carcinomatosis.	2009 Feb 14	19216794
Evaluation of the paclitaxel-ifosfamide-cisplatin (TIP) combination in relapsed and/or metastatic cervical cancer.	2009 Oct 6	19738606
The basophil activation test in the diagnosis of allergy: technical issues and critical factors.	2009 Sep	19243362
Permeability alterations after surgical trauma in normal rabbit peritoneum.	2010	20881404
10-year-old girl with severe edema caused by adder bite.	2010 Dec	20830658

Patents

Sample Use Guides

In Vivo Use Guide

Drops: Infants up to 1 year, 10-30 drops; Infants of 1 to 3 years, 30-45 drops; Children over 3 years, 45-60 drops; Adults, 60-120 drops. Syrup: Infants up to 1 year, 1-3 teaspoons; Infants of 1 to 3 years, 3-4 teaspoons; Children over 3 years, 4-6 teaspoons; Adults, 6-12 teaspoons. 1 teasponful Fenistil syrup = 5ml = 0.5mg Coated tablets: Adults, 3-6 tablets.

Route of Administration: Oral

In Vitro Use Guide

Experiments were carried out on isolated right ventricular papillary muscle of cat and guinea-pig, and on left atrial muscle of guinea-pig. The animals were anesthetized with ether, and the muscles were dissected from the heart as quickly as possible and mounted in an organ chamber. The preparations were driven electrically at 2.0 or 0.5 Hz. The transmembrane potentials were recorded by means of conventional glass microelectrode technique. The slow response APs were elicited with histamine (10^-5 M) ) or caffeine (2 mM) in partially depolarized (up to -40 mV) left atrial and right ventricular.myocardium of guinea-pigs. The membrane was depolarized by means of elevated K + (26 mM)-Krebs solution. Dimetindene was freshly dissolved and added to the organ chamber containing Krebs solution (composition in mM): NaC1 118, KCl 4.7, CaC12 2.5, NaH2PO4 1.0, MgC12 1.2, NaHCO3 24.9, glucose 11.5, which was gassed with 95% 02 and 5% CO2 and kept at 37C

Name

Type

Language

DIMETHINDENE MALEATE

Official Name

English

DIMETHINDENE MALEATE [USAN]

Common Name

English

DIMETINDENE MALEATE [MART.]

Common Name

English

2-[1-[2-[2-(Dimethylamino)ethyl]inden-3-yl]ethyl]pyridine maleate (1:1)

Systematic Name

English

DIMETINDENE MALEATE

Common Name

English

DIMETINDENE MALEATE [EP MONOGRAPH]

Common Name

English

DIMETHINDENE MALEATE [MI]

Common Name

English

DIMETINDENE MALEATE [JAN]

Common Name

English

SU-6518

Code

English

FORHISTAL MALEATE

Brand Name

English

1H-INDENE-2-ETHANAMINE, N,N-DIMETHYL-3-(1-(2-PYRIDINYL)ETHYL)-, (Z)-2-BUTENEDIOATE (1:1)

Systematic Name

English

DIMETHPYRINDENE MALEATE

Common Name

English

NSC-107677

Code

English

Dimetindene maleate [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29578