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=CC=CC=C12)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 316 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12593665	Antagonist 2849		0.692 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Urticaria 39 Sources: http://pcm.me/fenistil-%C2%AE/	Primary	Approved 8583	Fenistil Approved Use Unknown
Respiratory allergies 2 Sources: http://pcm.me/fenistil-%C2%AE/	Primary	Approved 8583	Fenistil Approved Use Unknown
Dermatoses 23 Sources: http://pcm.me/fenistil-%C2%AE/	Primary	Approved 8583	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 Health Status: unhealthy Age Group: 18 -69 Sex: M+F 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) Health Status: healthy Age Group: 33 (21-54) Sex: M+F 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 Health Status: healthy Age Group: adult Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/1773908/	Sources: https://pubmed.ncbi.nlm.nih.gov/1773908/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252		inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19663387/	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19663387/	yes [IC50 32.5 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 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
abcr GmbH	AB393645	http://www.abcr.com/shop/en/AB393645
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
eNovation Chemicals	D665175	https://www.enovationchem.com/ProductDetails.asp?ProductID=D665175
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

PubMed

Title	Date	PubMed
[Antimycobacterial antihistaminics].	1989 Aug	2513793
Are hypotension and rash after atracurium really caused by histamine release?	1994 May	7512805
[Antipruritic effect of antihistaminic and local anesthetic topical agents after iontophoretic histamine stimulation].	1996 May	8707580
[Mesenteric traction syndrome during the operation of aneurysms of the abdominal aorta--histamine release and prophylaxis with antihistaminics].	2003	14528656
Influence of peak measurement parameters on the quality of chiral electrophoretic separations.	2003 Aug	12900858
Structure-activity relationships of dimethindene derivatives as new M2-selective muscarinic receptor antagonists.	2003 Feb 27	12593665
Pruritic urticarial papules and plaques of pregnancy (PUPPP)--a case report.	2003 May-Jun	12891469
Effects of dimethindene maleate nasal spray on the quality of life in seasonal allergic rhinitis.	2003 Sep	14579656
Influence of methanol on the enantioresolution of antihistamines with carboxymethyl-beta-cyclodextrin in capillary electrophoresis.	2004 Aug	15352017
Premedication with H1 and H2 blocking agents reduces the incidence of postoperative nausea and vomiting.	2004 Aug	15338068
Anaphylaxis to intravenous sinistrin.	2004 Dec	15536136
[Prescription and safety of dimethindene maleate micropellet capsules in Hungary].	2004 Feb 15	15049047
Differential effects of organic modifiers on the enantioseparation of dimetindene maleate with carboxymethyl-beta-cyclodextrin in capillary electrophoresis.	2004 Jan	15335053
[Systemic mastocytosis. Classification, symptoms, therapy].	2004 Mar 15	15024485
Antimuscarinic agents exhibit local inhibitory effects on muscarinic receptors in bladder-afferent pathways.	2005 Feb	15708029
Acute ST-segment elevation myocardial infarction after amoxycillin-induced anaphylactic shock in a young adult with normal coronary arteries: a case report.	2005 Feb 25	15733315
A simplified premedication schedule for 1-hour paclitaxel administration.	2005 Jan-Feb	15724950
[Dimethindene determination in various dosage forms by means of capillary isotachophoresis].	2005 Sep	16209438
Safety of hydroxocobalamin in healthy volunteers in a randomized, placebo-controlled study.	2006	16990190
[Separation of dimetinden enantiomers in drugs by means of capillary isotachophoresis].	2006 Jan	16502809
Spectrophotometric determination of some antihistaminic drugs using 7,7,8,8-tetracyanoquinodimethane (TCNQ).	2006 Jan-Feb	16512227
Comparison of capillary zone electrophoresis and isotachophoresis determination of dimethindene enantiomers in pharmaceuticals using charged carboxyethyl-beta-cyclodextrin as a chiral selector.	2006 Nov	17200724
A simplified premedication protocol for one-hour paclitaxel infusion in various combinations.	2006 Nov	17072270
Analysis of enantiomers in biological matrices by charged cyclodextrin-mediated capillary zone electrophoresis in column-coupling arrangement with capillary isotachophoresis.	2006 Nov 15	18970848
[Aso an inspection of the family dog is warrented here].	2006 Oct 19	17621788
Characterization of antihistamine-human serum protein interactions by capillary electrophoresis.	2007 Apr 20	17339039
Determination of dimethindene enantiomers in pharmaceuticals by capillary electrophoresis with carboxyethyl-beta-cyclodextrin.	2007 Jan	17294809
[Quincke's edema: diagnosis and management of 102 patients with sudden upper airway obstruction].	2007 Jun	17487816
Chiral separation of alkylamine antihistamines in pharmaceuticals by capillary isotachophoresis with charged cyclodextrin.	2007 Nov	18058316
Rituximab therapy in Greek patients with rheumatoid arthritis.	2008 Dec	19707469
Anaphylactic shock caused by buffalo's mozzarella cheese.	2008 Jul	18683300
Antagonist affinity measurements at the Gi-coupled human histamine H3 receptor expressed in CHO cells.	2008 Jun 6	18538007
Treating common problems of the nose and throat in pregnancy: what is safe?	2008 May	18265995
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
Application of HILIC stationary phase to determination of dimethindene maleate in topical gel.	2009 Aug 15	19394784
Prevention of postoperative adhesion formation by individual and combined administration of 4 per cent icodextrin and dimetindene maleate.	2009 Dec	19918860
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
Characterization of novel selective H1-antihistamines for clinical evaluation in the treatment of insomnia.	2009 Sep 10	19663387
Permeability alterations after surgical trauma in normal rabbit peritoneum.	2010	20881404
Immunoglobulin E-mediated anaphylaxis to rabeprazole.	2010	20815321
Garlic-induced severe anaphylaxis in a nonatopic patient.	2010	20815318
Differential roles of M2 and M3 muscarinic receptor subtypes in modulation of bladder afferent activity in rats.	2010 Apr	20156651
10-year-old girl with severe edema caused by adder bite.	2010 Dec	20830658
Prevention of postoperative adhesion formation by individual and combined administration of 4 per cent icodextrin and dimetindene maleate (Br J Surg 2009; 96: 1476-1483).	2010 Mar	20140882
Urticaria, angioedema and dyspnoea in adjuvant therapy of melanoma with interferon alpha-2b.	2010 May	20526557
Identification of a novel selective H1-antihistamine with optimized pharmacokinetic properties for clinical evaluation in the treatment of insomnia.	2010 Oct 1	20800486
CD203c-based basophil activation test in allergy diagnosis: characteristics and differences to CD63 upregulation.	2010 Sep	20533392

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

DIMETINDENE MALEATE

Preferred Name

English

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 [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