Identification

Name
Rupatadine
Accession Number
DB11614
Type
Small Molecule
Groups
Approved
Description

Rupatadine is a dual histamine H1 receptor and platelet activating factor receptor antagonist that is used for symptomatic relief in seasonal and perennial rhinitis as well as chronic spontaneous urticaria. It was approved for marketing in Canada under the tradename Rupall and comes in tablet formulation for adult use and liquid formulation for pediatric use.

Structure
Thumb
Synonyms
  • Rupatadina
External IDs
UR-12592
Product Ingredients
IngredientUNIICASInChI Key
Rupatadine fumarateXJ6OT32M93182349-12-8JYBLCDXVHQWMSU-WLHGVMLRSA-N
Rupatadine trihydrochlorideG61C8NZY2T156611-76-6BQFOTHHRVVHLEW-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RupallTablet10 mgOralPediapharm Inc2017-01-16Not applicableCanada
RupallSolution1 mgOralPediapharm Inc2017-01-20Not applicableCanada
Categories
UNII
2AE8M83G3E
CAS number
158876-82-5
Weight
Average: 415.97
Monoisotopic: 415.1815255
Chemical Formula
C26H26ClN3
InChI Key
WUZYKBABMWJHDL-UHFFFAOYSA-N
InChI
InChI=1S/C26H26ClN3/c1-18-13-19(16-28-15-18)17-30-11-8-20(9-12-30)25-24-7-6-23(27)14-22(24)5-4-21-3-2-10-29-26(21)25/h2-3,6-7,10,13-16H,4-5,8-9,11-12,17H2,1H3
IUPAC Name
13-chloro-2-{1-[(5-methylpyridin-3-yl)methyl]piperidin-4-ylidene}-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3(8),4,6,11,13-hexaene
SMILES
CC1=CC(CN2CCC(CC2)=C2C3=CC=C(Cl)C=C3CCC3=C2N=CC=C3)=CN=C1

Pharmacology

Indication

For the symptomatic relief of nasal and non-nasal symptoms of seasonal allergic rhinitis and perennial allergic rhinitis in patients 2 years of age and older [Label]. Also used for the symptomatic relief of chronic spontaneous urticaria in patients 2 years of age and older.

Associated Conditions
Pharmacodynamics

Rupatadine is an anti allergenic and acts to reduce allergic symptoms like urticaria, rhinorrhea, sneezing and itching [Label].

Mechanism of action

Rupatadine is a dual histamine H1 receptor and platelet activating (PAF) receptor antagonist [1] [Label]. During allergic response mast cells undergo degranulation, releasing histamine and other substances [2]. Histamine acts on H1 receptors to produce symptoms of nasal blockage, rhinorhea, itching, and swelling. PAF is produced from phospholipids cleaved by phospholipase A2. It acts to produce vascular leakage which contributes to rhinorhea and nasal blockage. By blocking both the H1 receptor and PAF receptor, rupatidine prevents these mediators from exerting their effects and so reduces the severity of allergic symptoms.

TargetActionsOrganism
APlatelet-activating factor receptor
antagonist
Human
AHistamine H1 receptor
antagonist
Human
Absorption

Rupatidine is rapidly absorbed with a Tmax of 1 h [Label]. Administration with a high fat meal increases exposure by 23% and increases Tmax to 2 h.

Volume of distribution

The apparent volume of distribution is 9799 L [Label].

Protein binding

Rupatidine is 98.5-99.0% bound to human plasma proteins [Label].

Metabolism

Rupatadine is metabolized by oxidation mediated primarily by CYP3A4 [Label]. CYP2C9, CYP2C19, and CYP2D6 are also involved to a lesser extent. The metabolites desloratidine and hydroxylated forms of desloratidine retain some activity as H1 receptor antagonists.

Route of elimination
Not Available
Half life

The half life of elimination is 15.9 h in children 2-5 years old, 12.3 h in children 6-11 years old, 5.9 h in adults, and 8.7 h in geriatric patients [Label].

Clearance

Systemic clearance is 1556.2 L/h in young adults and 798.2 L/h in geriatric patients [Label].

Toxicity
Not Available
Affected organisms
Not Available
Pathways
PathwayCategory
Rupatadine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Rupatadine can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Rupatadine.
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Rupatadine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Rupatadine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Rupatadine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Rupatadine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Rupatadine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Rupatadine.
4-MethoxyamphetamineThe metabolism of Rupatadine can be decreased when combined with 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of Rupatadine can be decreased when combined with 5-androstenedione.
Food Interactions
Not Available

References

General References
  1. Merlos M, Giral M, Balsa D, Ferrando R, Queralt M, Puigdemont A, Garcia-Rafanell J, Forn J: Rupatadine, a new potent, orally active dual antagonist of histamine and platelet-activating factor (PAF). J Pharmacol Exp Ther. 1997 Jan;280(1):114-21. [PubMed:8996188]
  2. Alfaro V: Role of histamine and platelet-activating factor in allergic rhinitis. J Physiol Biochem. 2004 Jun;60(2):101-11. [PubMed:15457928]
External Links
Human Metabolome Database
HMDB0240234
PubChem Compound
133017
PubChem Substance
347828008
ChemSpider
117388
BindingDB
50036935
ChEBI
135673
ChEMBL
CHEMBL91397
PharmGKB
PA165107052
Wikipedia
Rupatadine
ATC Codes
R06AX28 — Rupatadine
AHFS Codes
  • 04:08.00 — Second Generation Antihistamines
FDA label
Download (794 KB)
MSDS
Download (56.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHuman Experimentation (Human Volunteers)1
2CompletedTreatmentCold Contact Urticaria1
2TerminatedTreatmentUrticarias1
3RecruitingTreatmentChronic Urticaria1
3TerminatedTreatmentUrticarias1
4TerminatedPreventionHealthy Volunteers1
4Unknown StatusPreventionAllergies1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionOral1 mg
TabletOral10 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)194-201FDA Label
logP0.8FDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.00544 mg/mLALOGPS
logP4.82ALOGPS
logP5.37ChemAxon
logS-4.9ALOGPS
pKa (Strongest Basic)7.19ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area29.02 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity133.83 m3·mol-1ChemAxon
Polarizability46.98 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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 benzocycloheptapyridines. These are aromatic compounds containing a benzene ring and a pyridine ring fused to a seven membered carbocycle.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzocycloheptapyridines
Sub Class
Not Available
Direct Parent
Benzocycloheptapyridines
Alternative Parents
Methylpyridines / Aralkylamines / Piperidines / Benzenoids / Aryl chlorides / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organochlorides
show 1 more
Substituents
Benzocycloheptapyridine / Methylpyridine / Aralkylamine / Aryl chloride / Aryl halide / Piperidine / Benzenoid / Pyridine / Heteroaromatic compound / Tertiary aliphatic amine
show 10 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Platelet activating factor receptor activity
Specific Function
Receptor for platelet activating factor, a chemotactic phospholipid mediator that possesses potent inflammatory, smooth-muscle contractile and hypotensive activity. Seems to mediate its action via ...
Gene Name
PTAFR
Uniprot ID
P25105
Uniprot Name
Platelet-activating factor receptor
Molecular Weight
39203.075 Da
References
  1. Merlos M, Giral M, Balsa D, Ferrando R, Queralt M, Puigdemont A, Garcia-Rafanell J, Forn J: Rupatadine, a new potent, orally active dual antagonist of histamine and platelet-activating factor (PAF). J Pharmacol Exp Ther. 1997 Jan;280(1):114-21. [PubMed:8996188]
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. Merlos M, Giral M, Balsa D, Ferrando R, Queralt M, Puigdemont A, Garcia-Rafanell J, Forn J: Rupatadine, a new potent, orally active dual antagonist of histamine and platelet-activating factor (PAF). J Pharmacol Exp Ther. 1997 Jan;280(1):114-21. [PubMed:8996188]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Rupatadine Canadian Prescribing Information [File]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da

Drug created on August 05, 2016 17:52 / Updated on November 18, 2018 13:31