Identification

Name
Dimetindene
Accession Number
DB08801
Type
Small Molecule
Groups
Approved, Investigational
Description

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

Structure
Thumb
Synonyms
  • Dimethindene
Product Ingredients
IngredientUNIICASInChI Key
Dimetindene maleate6LL60J9E0O3614-69-5SWECWXGUJQLXJF-BTJKTKAUSA-N
International/Other Brands
Fenistil (Novartis) / Foristal (Novartis) / Vibrocil (Novartis)
Categories
UNII
661FH77Z3P
CAS number
5636-83-9
Weight
Average: 292.418
Monoisotopic: 292.193948778
Chemical Formula
C20H24N2
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

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.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
AMuscarinic acetylcholine receptor M2
antagonist
Human
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
PathwayCategory
Dimetindene H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Dimetindene.Experimental, Illicit
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Dimetindene.Experimental
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Dimetindene.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Dimetindene.Experimental, Illicit
AmphetamineAmphetamine may decrease the sedative activities of Dimetindene.Approved, Illicit, Investigational
BenzphetamineBenzphetamine may decrease the sedative activities of Dimetindene.Approved, Illicit
Benzylpenicilloyl PolylysineDimetindene may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Dimetindene.Approved, Investigational
ChlorphentermineChlorphentermine may decrease the sedative activities of Dimetindene.Illicit, Withdrawn
DextroamphetamineDextroamphetamine may decrease the sedative activities of Dimetindene.Approved, Illicit
DiethylpropionDiethylpropion may decrease the sedative activities of Dimetindene.Approved, Illicit
GepefrineGepefrine may decrease the sedative activities of Dimetindene.Experimental
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Dimetindene.Approved, Investigational
HydroxyamphetamineHydroxyamphetamine may decrease the sedative activities of Dimetindene.Approved
Iofetamine I-123Iofetamine I-123 may decrease the sedative activities of Dimetindene.Approved
LisdexamfetamineLisdexamfetamine may decrease the sedative activities of Dimetindene.Approved, Investigational
MephedroneMephedrone may decrease the sedative activities of Dimetindene.Investigational
MephentermineMephentermine may decrease the sedative activities of Dimetindene.Approved
MethamphetamineMethamphetamine may decrease the sedative activities of Dimetindene.Approved, Illicit
MethoxyphenamineMethoxyphenamine may decrease the sedative activities of Dimetindene.Experimental
MidomafetamineMidomafetamine may decrease the sedative activities of Dimetindene.Experimental, Illicit, Investigational
MMDAMMDA may decrease the sedative activities of Dimetindene.Experimental, Illicit
PhenterminePhentermine may decrease the sedative activities of Dimetindene.Approved, Illicit
PseudoephedrinePseudoephedrine may decrease the sedative activities of Dimetindene.Approved
RitobegronRitobegron may decrease the sedative activities of Dimetindene.Investigational
Food Interactions
Not Available

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. [PubMed:10069503]
External Links
Human Metabolome Database
HMDB0015691
KEGG Drug
D07853
PubChem Compound
21855
PubChem Substance
99445271
ChemSpider
20541
BindingDB
81452
ChEBI
135222
ChEMBL
CHEMBL22108
PharmGKB
PA165958420
Wikipedia
Dimetindene
ATC Codes
D04AA13 — DimetindeneR06AB03 — Dimetindene
MSDS
Download (72.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedTreatmentAtopic Dermatitis (AD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
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

Taxonomy

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
Indene / Pyridine / Heteroaromatic compound / Tertiary aliphatic amine / Tertiary amine / Azacycle / Organoheterocyclic compound / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Details
1. Histamine H1 receptor
Kind
Protein
Organism
Human
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. [PubMed:20800486]
  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:8608784]
Kind
Protein
Organism
Human
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. [PubMed:8608784]

Drug created on October 15, 2010 09:48 / Updated on June 02, 2018 09:32