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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
Dimethindene
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
FenistilNovartis
ForistalNovartis
VibrocilNovartis
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Dimetindene maleate
ThumbNot applicableDBSALT000908
Categories
UNII661FH77Z3P
CAS number5636-83-9
WeightAverage: 292.418
Monoisotopic: 292.193948778
Chemical FormulaC20H24N2
InChI KeyInChIKey=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
Taxonomy
ClassificationNot classified
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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
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
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
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 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 RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot 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
ATC CodesD04AA13R06AB03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (72.8 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
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 action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then trigge...
Gene Name:
CHRM2
Uniprot ID:
P08172
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 ]
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Drug created on October 15, 2010 09:48 / Updated on August 17, 2016 12:24