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Identification
NameDimetindene
Accession NumberDB08801
Typesmall molecule
Groupsapproved
Description

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

Structure
Thumb
Synonyms
SynonymLanguageCode
DimethindeneNot AvailableNot Available
Salts
Name/CAS Structure Properties
Dimetindene maleate
Thumb Not applicable DBSALT000908
Brand names
NameCompany
FenistilNovartis
ForistalNovartis
VibrocilNovartis
Brand mixturesNot Available
Categories
CAS number5636-83-9
WeightAverage: 292.418
Monoisotopic: 292.193948778
Chemical FormulaC20H24N2
InChI KeyMVMQESMQSYOVGV-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
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassIndenes and Isoindenes
SubclassNot Available
Direct parentIndenes and Isoindenes
Alternative parentsBenzene and Substituted Derivatives; Pyridines and Derivatives; Tertiary Amines; Polyamines
Substituentsbenzene; pyridine; tertiary amine; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the indenes and isoindenes. These are compounds conaining an indene moiety(which consists of a cyclopentadiene fused to a benzene ring), or a isoindene moiety (which consists of a cyclopentadiene fused to cyclohezadiene ring).
Pharmacology
IndicationIndicated 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.
PharmacodynamicsDimethindene 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 actionDimethindene 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityAs 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9924
Blood Brain Barrier + 0.9643
Caco-2 permeable + 0.7598
P-glycoprotein substrate Substrate 0.7931
P-glycoprotein inhibitor I Inhibitor 0.8852
P-glycoprotein inhibitor II Inhibitor 0.6697
Renal organic cation transporter Inhibitor 0.7693
CYP450 2C9 substrate Non-substrate 0.8291
CYP450 2D6 substrate Substrate 0.6025
CYP450 3A4 substrate Substrate 0.7558
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Inhibitor 0.895
CYP450 2D6 substrate Inhibitor 0.8932
CYP450 2C19 substrate Inhibitor 0.8994
CYP450 3A4 substrate Non-inhibitor 0.8308
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5637
Ames test Non AMES toxic 0.5454
Carcinogenicity Non-carcinogens 0.9431
Biodegradation Not ready biodegradable 0.9888
Rat acute toxicity 2.7060 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7746
hERG inhibition (predictor II) Inhibitor 0.639
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
CapsuleOral4mg
LiquidTopical0.1g/100mL
SyrupOral0.01g/100mL
Tablet, coatedOral1mg
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point158Huebner, C.F.; U S . Patent 2,970,149; January 31, 1961; assigned to Ciba Pharmaceutical Products, Inc.
water solubility239 mg/L (at 37 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
Predicted Properties
PropertyValueSource
water solubility3.84e-02 g/lALOGPS
logP4.03ALOGPS
logP3.74ChemAxon
logS-3.9ALOGPS
pKa (strongest acidic)18.93ChemAxon
pKa (strongest basic)9.7ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count0ChemAxon
polar surface area16.13ChemAxon
rotatable bond count5ChemAxon
refractivity93.57ChemAxon
polarizability34.9ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Huebner, C.F.; U S . Patent 2,970,149; January 31, 1961; assigned to Ciba Pharmaceutical Products, Inc.

General Reference
  1. 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
  2. Novartis Pamphlet
External Links
ResourceLink
KEGG DrugD07853
ChemSpider20541
PharmGKBPA165958420
WikipediaDimetindene
ATC CodesD04AA13R06AB03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(72.8 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Histamine H1 receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Histamine H1 receptor P35367 Details

References:

  1. 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
  2. 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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M2 P08172 Details

References:

  1. 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

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Drug created on October 15, 2010 09:48 / Updated on April 14, 2014 15:19