Dimetindene

Identification

Summary

Dimetindene is a 1st generation selective H1 antagonist used topically as an antipruritic and orally to treat allergies.

Generic Name
Dimetindene
DrugBank Accession Number
DB08801
Background

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

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 292.418
Monoisotopic: 292.193948778
Chemical Formula
C20H24N2
Synonyms
  • Dimethindene
  • Dimetindene
  • Dimetindeno

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.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Humans
AMuscarinic acetylcholine receptor M2
antagonist
Humans
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

Adverse Effects
Adverseeffects
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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.

Pathways
PathwayCategory
Dimetindene H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-Benzodiazepine1,2-Benzodiazepine may increase the central nervous system depressant (CNS depressant) activities of Dimetindene.
AcetazolamideAcetazolamide may increase the central nervous system depressant (CNS depressant) activities of Dimetindene.
AcetophenazineAcetophenazine may increase the central nervous system depressant (CNS depressant) activities of Dimetindene.
AclidiniumThe risk or severity of adverse effects can be increased when Dimetindene is combined with Aclidinium.
AdenosineThe risk or severity of Tachycardia can be increased when Adenosine is combined with Dimetindene.
AgomelatineAgomelatine may increase the central nervous system depressant (CNS depressant) activities of Dimetindene.
AlfentanilThe risk or severity of adverse effects can be increased when Dimetindene is combined with Alfentanil.
AlimemazineAlimemazine may increase the central nervous system depressant (CNS depressant) activities of Dimetindene.
AlloinThe therapeutic efficacy of Alloin can be decreased when used in combination with Dimetindene.
AlmotriptanAlmotriptan may increase the central nervous system depressant (CNS depressant) activities of Dimetindene.
Interactions
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Food Interactions
Not Available

Products

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Product Ingredients
IngredientUNIICASInChI Key
Dimetindene maleate6LL60J9E0O3614-69-5SWECWXGUJQLXJF-BTJKTKAUSA-N
International/Other Brands
Fenistil (Novartis) / Foristal (Novartis) / Vibrocil (Novartis)
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
เฟนีสติล เจลGel0.1 %w/wTopicalบริษัท แกล็กโซสมิทไคล์น คอนซูมเมอร์ เฮลธ์แคร์ (ประเทศไทย) จำกัด2016-04-25Not applicableThailand flag

Categories

ATC Codes
R06AB03 — DimetindeneD04AA13 — Dimetindene
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as indenes and isoindenes. These are compounds containing an indene moiety(which consists of a cyclopentadiene fused to a benzene ring), or a isoindene moiety (which consists of a cyclopentadiene fused to cyclohexadiene ring).
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Indenes and isoindenes
Sub Class
Not Available
Direct Parent
Indenes and isoindenes
Alternative Parents
Pyridines and derivatives / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Amine / Aromatic heteropolycyclic compound / Azacycle / Heteroaromatic compound / Hydrocarbon derivative / Indene / Organic nitrogen compound / Organoheterocyclic compound / Organonitrogen compound / Organopnictogen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
661FH77Z3P
CAS number
5636-83-9
InChI Key
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
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

References

Synthesis Reference

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

General References
  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. [Article]
Human Metabolome Database
HMDB0015691
KEGG Drug
D07853
PubChem Compound
21855
PubChem Substance
99445271
ChemSpider
20541
BindingDB
81452
RxNav
3449
ChEBI
135222
ChEMBL
CHEMBL22108
PharmGKB
PA165958420
Wikipedia
Dimetindene
MSDS
Download (72.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentNasal Congestion / Rhinorrhoea / Sneezing / Upper Respiratory Tract Infection1
1, 2WithdrawnNot AvailableArrhythmia / Blood Pressures / Heart Rate1
Not AvailableCompletedTreatmentDermatitis, Dermatitis Atopic1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Capsule, extended release4 MG
EmulsionTopical0.1 %
GelTopical0.1 %
GelTopical30 G
SolutionOral1 mg
Solution / dropsOral1 MG/ML
Solution / drops; suspension / drops
TabletOral1 mg
Tablet, coatedOral
Tablet, coatedOral1 MG
Tablet, sugar coatedOral1 mg
GelTopical
Solution / dropsOral
Tablet, sugar coatedOral
GelTopical1 mg/g
SolutionOral1 mg/mL
Injection, solutionParenteral
SprayNasal
Solution / drops; suspension / dropsNasal
GelTopical0.1 %w/w
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)158Huebner, 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 Solubility0.0384 mg/mLALOGPS
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 Area16.13 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity93.57 m3·mol-1ChemAxon
Polarizability34.9 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9924
Blood Brain Barrier+0.9643
Caco-2 permeable+0.7598
P-glycoprotein substrateSubstrate0.7931
P-glycoprotein inhibitor IInhibitor0.8852
P-glycoprotein inhibitor IIInhibitor0.6697
Renal organic cation transporterInhibitor0.7693
CYP450 2C9 substrateNon-substrate0.8291
CYP450 2D6 substrateSubstrate0.6025
CYP450 3A4 substrateSubstrate0.7558
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorInhibitor0.895
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5637
Ames testNon AMES toxic0.5454
CarcinogenicityNon-carcinogens0.9431
BiodegradationNot ready biodegradable0.9888
Rat acute toxicity2.7060 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7746
hERG inhibition (predictor II)Inhibitor0.639
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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Details
1. Histamine H1 receptor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
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 catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
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. doi: 10.1016/j.bmcl.2010.07.117. Epub 2010 Aug 3. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
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. [Article]

Drug created on October 15, 2010 15:48 / Updated on June 16, 2021 12:31