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
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.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination for symptomatic treatment ofAcute sinusitisCombination Product in combination with: Phenylephrine (DB00388)•••••••••••••••• ••••••••• •••••••• • •••••• •••••
Treatment ofAllergies•••••••••••••••• ••••••••• ••••••• ••••••• ••••••
Treatment ofAnaphylaxis•••••••••••••••••••••
Prevention ofAnaphylaxis caused by anaesthesia therapy•••••••••••••••••••••
Used in combination for symptomatic treatment ofChronic rhinitisCombination Product in combination with: Phenylephrine (DB00388)•••••••••••••••• ••••••••• •••••••• • •••••• •••••
Contraindications & Blackbox Warnings
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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
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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
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.
AlbuterolThe risk or severity of Tachycardia can be increased when Salbutamol is combined with Dimetindene.
AlfentanilThe risk or severity of adverse effects can be increased when Dimetindene is combined with Alfentanil.
AlloinThe therapeutic efficacy of Alloin can be decreased when used in combination with Dimetindene.
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
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Vibrocil NasensprayDimetindene maleate (0.25 mg) + Phenylephrine (2.5 mg)SprayNasalGsk Gebro Consumer Healthcare Gmb H1990-07-25Not applicableAustria flag
Vibrocil NasentropfenDimetindene maleate (0.25 mg) + Phenylephrine (2.5 mg)Solution / drops; Suspension / dropsNasalGsk Gebro Consumer Healthcare Gmb H1985-08-09Not applicableAustria 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
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PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedTreatmentAtopic Dermatitis1somestatusstop reasonjust information to hide
3CompletedTreatmentNasal Congestion / Rhinorrhoea / Sneezing / Upper Respiratory Tract Infection1somestatusstop reasonjust information to hide
1, 2WithdrawnNot AvailableArrhythmia / Blood Pressures / Heart Rates1somestatusstop reasonjust information to hide

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 / drops1 MG/ML
TabletOral1 mg
Tablet, coatedOral
Tablet, coatedOral1 MG
Tablet, sugar coatedOral1 mg
GelTopical1 mg/g
SolutionOral1 mg/mL
Injection, solutionParenteral1 mg/ml
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)18.19Chemaxon
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
Polarizability34.99 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-MSsplash10-0a6r-9580000000-d988cb2b7d041f1d29b4
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-052f-2390000000-716e195bbe4ee3452dd1
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000f-0690000000-d2f35eab733f1e6d7c5b
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0pb9-1940000000-93792a02dd1b0776a3bc
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-054o-3930000000-3b156432deb7e97f3f55
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-052f-9610000000-26c1a7713b0284fad382
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-0900000000-5bc8b7c5fd03588a0117
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-186.9898261
predicted
DarkChem Lite v0.1.0
[M-H]-169.48335
predicted
DeepCCS 1.0 (2019)
[M+H]+187.7801261
predicted
DarkChem Lite v0.1.0
[M+H]+171.84134
predicted
DeepCCS 1.0 (2019)
[M+Na]+187.3687261
predicted
DarkChem Lite v0.1.0
[M+Na]+177.93446
predicted
DeepCCS 1.0 (2019)

Targets

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Details
1. Histamine H1 receptor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
G-protein-coupled receptor for histamine, a biogenic amine that functions as an immune modulator and a neurotransmitter (PubMed:33828102, PubMed:8280179). Through the H1 receptor, histamine mediates the contraction of smooth muscles and increases capillary permeability due to contraction of terminal venules. Also mediates neurotransmission in the central nervous system and thereby regulates circadian rhythms, emotional and locomotor activities as well as cognitive functions (By similarity)
Specific Function
G protein-coupled serotonin receptor activity
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]
  3. Horak F, Unkauf M, Beckers C, Mittermaier EM: Efficacy and tolerability of intranasally applied dimetindene maleate solution versus placebo in the treatment of seasonal allergic rhinitis. Arzneimittelforschung. 2000 Dec;50(12):1099-105. doi: 10.1055/s-0031-1300341. [Article]
  4. Rehn D, Geissler H, Schonbrunn U, Lukas H, Hennings G: Effect-time-relation of the H1-receptor antagonist dimethindene maleate following intravenous injection. Agents Actions. 1990 Apr;30(1-2):178-81. doi: 10.1007/BF01969031. [Article]
  5. Rehn D, Haack D, Vecsei P, Hennings G: The influence of dimetindene maleate on the endogenous hydrocortisone synthesis suppressing potency of betamethasone. Arzneimittelforschung. 1985;35(6):970-2. [Article]
  6. Duda D, Lorenz W, Celik I: Histamine release in mesenteric traction syndrome during abdominal aortic aneurysm surgery: prophylaxis with H1 and H2 antihistamines. Inflamm Res. 2002 Oct;51(10):495-9. doi: 10.1007/pl00012418. [Article]
  7. Schaffler K, Wauschkuhn CH, Brunnauer H, Rehn D: Evaluation of the local anaesthetic activity of dimetindene maleate by means of laser algesimetry in healthy volunteers. Arzneimittelforschung. 1992 Nov;42(11):1332-5. [Article]
  8. Rubinstein R, Nissenkorn I, Cohen S: Acetylcholine mediation of the contractile response to histamine in human bladder detrusor muscle. Eur J Pharmacol. 1987 Oct 6;142(1):45-50. doi: 10.1016/0014-2999(87)90652-2. [Article]
  9. Kirchhoff CH, Kremer B, Haaf-von Below S, Kyrein HJ, Mosges R: Effects of dimethindene maleate nasal spray on the quality of life in seasonal allergic rhinitis. Rhinology. 2003 Sep;41(3):159-66. [Article]
  10. Humphreys F, Shuster S: The effect of topical dimethindene maleate on weal reactions. Br J Clin Pharmacol. 1987 Feb;23(2):234-6. doi: 10.1111/j.1365-2125.1987.tb03035.x. [Article]
  11. Doenicke A, Moss J, Lorenz W, Hoernecke R, Gottardis M: Are hypotension and rash after atracurium really caused by histamine release? Anesth Analg. 1994 May;78(5):967-72. doi: 10.1213/00000539-199405000-00023. [Article]
  12. Rehn D, Geissler H, Schuster O, Lukas H, Hennings G: Effect-kinetic characterization of dimethindene maleate following oral administration (Fenistil, Tropfen). Fundam Clin Pharmacol. 1990;4(6):673-83. doi: 10.1111/j.1472-8206.1990.tb00047.x. [Article]
  13. Casy AF, Drake AF, Ganellin CR, Mercer AD, Upton C: Stereochemical studies of chiral H-1 antagonists of histamine: the resolution, chiral analysis, and biological evaluation of four antipodal pairs. Chirality. 1992;4(6):356-66. doi: 10.1002/chir.530040606. [Article]
  14. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General 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 triggers calcium ion release into the cytosol
Specific Function
arrestin family protein binding
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 at October 15, 2010 15:48 / Updated at October 30, 2024 22:59