DrugBank: Dimethindene (DB08801)

targets (2)

Identification

Name

Dimethindene

Accession Number

DB08801

Type

small molecule

Groups

approved

Description

Dimetindene (Fenistil) is an antihistamine/anticholinergic used orally and locally as an antipruritic.

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

(±)-Dimethindene
Dimethylpyrindene

Salts

Not Available

Brand names

Name	Company
Fengel
Fenistil	Novartis
Foristal
Pecofenil
Triten

Brand mixtures

Not Available

Categories

Antipruritics
Anti-Allergic Agents
Antihistamines
Anticholinergics

CAS number

5636-83-9

Weight

Average: 292.418
Monoisotopic: 292.193948778

Chemical Formula

C₂₀H₂₄N₂

InChI Key

InChIKey=MVMQESMQSYOVGV-UHFFFAOYSA-N

InChI

InChI=1S/C20H24N2/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/h4-10,12,15H,11,13-14H2,1-3H3

Plain Text

IUPAC Name

dimethyl(2-{3-[1-(pyridin-2-yl)ethyl]-1H-inden-2-yl}ethyl)amine

SMILES

CC(C1=C(CCN(C)C)CC2=CC=CC=C12)C1=CC=CC=N1

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Not Available

Substructures

Not Available

Pharmacology

Indication

Indicated as symptomatic treatment of allergic reactions: urticaria, allergies of the upper respiratory tract such as hey fever and perennial rhinitis, food and drug allergies; pruritus of various origins, except pruritus due to cholestasis; insect bites. Dimethindene is also indicated for pruritus in eruptive skin diseases such as chicken-pox. Dimethindene can also be used as an adjuvant in eczema and other pruriginous dermatoses of allergic origin.

Pharmacodynamics

Dimethindene occurs as a racemic mixture. The (S)-(+)-dimethindene is a potent M2-selective muscarinic receptor antagonist (with lower affinity for M1, M3, and M4 muscarinic receptors). The (R)-(-)-enantiomer is the eutomer (responsible for bioactivity) for histamine H1 receptor binding.

Mechanism of action

Dimethindene is a selective histamine H1 antagonist and 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.

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half life

Not Available

Clearance

Not Available

Toxicity

As with other antihistaminic drugs, overdosage can produce the following symptoms: CNS depression accompanied by drowsiness (especially in adults), CNS stimulation and antimuscarinic effects (especially in children) including the following: excitation, ataxia, hallucinations, tonic or clonic spasms, mydriasis, dryness of the mouth, redness of the face, urine retention, fever and tachycardia. Blood hypotension is also possible. In its terminal phase, coma can be aggravated by cardiorespiratory colapse and death. There has been no report of a fatal outcome of Dimethindene overdosage.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Form	Route	Strength
Capsule	Oral	4mg
Liquid	Topical	0.1g/100mL
Syrup	Oral	0.01g/100mL
Tablet, coated	Oral	1mg

Prices

Not Available

Patents

Not Available

Properties

State

solid

Experimental Properties

Property	Value	Source
water solubility	239 mg/L (at 37 °C)	YALKOWSKY,SH & DANNENFELSER,RM (1992)

Predicted Properties

Property	Value	Source
water solubility	3.84e-02 g/l	ALOGPS
logP	4.03	ALOGPS
logP	3.74	ChemAxon
logS	-3.9	ALOGPS
pKa (strongest acidic)	18.93	ChemAxon
pKa (strongest basic)	9.7	ChemAxon
physiological charge	1	ChemAxon
hydrogen acceptor count	2	ChemAxon
hydrogen donor count	0	ChemAxon
polar surface area	16.13	ChemAxon
rotatable bond count	5	ChemAxon
refractivity	93.57	ChemAxon
polarizability	34.9	ChemAxon

References

Synthesis Reference

Not Available

General Reference

Lambrecht G, Gross J, Mutschler E: Neuronal soma-dendritic and prejunctional M1-M4 receptors in gastrointestinal and genitourinary smooth muscle. Life Sci. 1999;64(6-7):403-10. Pubmed
Novartis Pamphlet

External Links

Resource	Link
KEGG Drug	D07853
ChemSpider	20541
ChEBI	126443
ChEMBL	126443
PharmGKB	PA165958420
Wikipedia	http://en.wikipedia.org/wiki/Dimetindene

ATC Codes

D04AA13
R06AB03

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

show (72.8 KB)

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. Histamine H1 receptor Pharmacological action: yes Actions: antagonist In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system Organism class: human UniProt ID: P35367 Gene: HRH1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Moree WJ, Li BF, Zamani-Kord S, Yu J, Coon T, Huang C, Marinkovic D, Tucci FC, Malany S, Bradbury MJ, Hernandez LM, Wen J, Wang H, Hoare SR, Petroski RE, Jalali K, Yang C, Sacaan A, Madan A, Crowe PD, Beaton G: Identification of a novel selective H1-antihistamine with optimized pharmacokinetic properties for clinical evaluation in the treatment of insomnia. Bioorg Med Chem Lett. 2010 Oct 1;20(19):5874-8. Epub 2010 Aug 3. Pubmed Pfaff O, Hildebrandt C, Waelbroeck M, Hou X, Moser U, Mutschler E, Lambrecht G: The (S)-(+)-enantiomer of dimethindene: a novel M2-selective muscarinic receptor antagonist. Eur J Pharmacol. 1995 Nov 24;286(3):229-40. Pubmed 2. Muscarinic acetylcholine receptor M2 Pharmacological action: yes Actions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition Organism class: human UniProt ID: P08172 Gene: CHRM2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Pfaff O, Hildebrandt C, Waelbroeck M, Hou X, Moser U, Mutschler E, Lambrecht G: The (S)-(+)-enantiomer of dimethindene: a novel M2-selective muscarinic receptor antagonist. Eur J Pharmacol. 1995 Nov 24;286(3):229-40. Pubmed

Targets

1. Histamine H1 receptor

Pharmacological action: yes
Actions: antagonist

In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system

Organism class: human
UniProt ID: P35367 Link_out

Gene: HRH1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Moree WJ, Li BF, Zamani-Kord S, Yu J, Coon T, Huang C, Marinkovic D, Tucci FC, Malany S, Bradbury MJ, Hernandez LM, Wen J, Wang H, Hoare SR, Petroski RE, Jalali K, Yang C, Sacaan A, Madan A, Crowe PD, Beaton G: Identification of a novel selective H1-antihistamine with optimized pharmacokinetic properties for clinical evaluation in the treatment of insomnia. Bioorg Med Chem Lett. 2010 Oct 1;20(19):5874-8. Epub 2010 Aug 3. Pubmed
Pfaff O, Hildebrandt C, Waelbroeck M, Hou X, Moser U, Mutschler E, Lambrecht G: The (S)-(+)-enantiomer of dimethindene: a novel M2-selective muscarinic receptor antagonist. Eur J Pharmacol. 1995 Nov 24;286(3):229-40. Pubmed

2. Muscarinic acetylcholine receptor M2

Pharmacological action: yes
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition

Organism class: human
UniProt ID: P08172 Link_out

Gene: CHRM2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Pfaff O, Hildebrandt C, Waelbroeck M, Hou X, Moser U, Mutschler E, Lambrecht G: The (S)-(+)-enantiomer of dimethindene: a novel M2-selective muscarinic receptor antagonist. Eur J Pharmacol. 1995 Nov 24;286(3):229-40. Pubmed

Comments

Drug created on October 15, 2010 09:48 / Updated on February 08, 2013 16:27