Identification

Name
Alcaftadine
Accession Number
DB06766
Type
Small Molecule
Groups
Approved
Description

Alcaftadine is a H1 histamine receptor antagonist indicated for the prevention of itching associated with allergic conjunctivitis. This drug was approved in July 2010.

Structure
Thumb
Synonyms
  • 6,11-Dihydro-11-(1-Methyl-4-piperidinylidene)-5H-iMidazo[2,1-b][3]benzazepine-3-carboxaldehyde
  • Alcaftadina
  • Alcaftadinum
  • Vilasta
External IDs
R 89674 / R-89674
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LastacaftSolution / drops2.5 mg/mLOphthalmicRebel Distributors2010-11-01Not applicableUs
LastacaftSolution / drops2.5 mg/mLOphthalmicAllergan2010-11-01Not applicableUs
LastacaftSolution / drops2.5 mg/mLOphthalmicPhysicians Total Care, Inc.2011-08-19Not applicableUs
International/Other Brands
Lastacaft
Categories
UNII
7Z8O94ECSX
CAS number
147084-10-4
Weight
Average: 307.3895
Monoisotopic: 307.168462309
Chemical Formula
C19H21N3O
InChI Key
MWTBKTRZPHJQLH-UHFFFAOYSA-N
InChI
InChI=1S/C19H21N3O/c1-21-9-6-15(7-10-21)18-17-5-3-2-4-14(17)8-11-22-16(13-23)12-20-19(18)22/h2-5,12-13H,6-11H2,1H3
IUPAC Name
2-(1-methylpiperidin-4-ylidene)-4,7-diazatricyclo[8.4.0.0³,⁷]tetradeca-1(14),3,5,10,12-pentaene-6-carbaldehyde
SMILES
CN1CCC(CC1)=C1C2=NC=C(C=O)N2CCC2=CC=CC=C12

Pharmacology

Indication

For the prevention of itching associated with allergic conjunctivitis.

Associated Conditions
Pharmacodynamics

Following bilateral topical ocular administration of alcaftadine ophthalmic solution, 0.25%, the mean plasma Cmax of alcaftadine was approximately 60 pg/mL and the median Tmax occurred at 15 minutes. Plasma concentrations of alcaftadine were below the lower limit of quantification (10 pg/mL) by 3 hours after dosing. The mean Cmax of the active carboxylic acid metabolite was approximately 3 ng/mL and occurred at 1 hour after dosing. Plasma concentrations of the carboxylic acid metabolite were below the lower limit of quantification (100 pg/mL) by 12 hours after dosing.

Mechanism of action

Alcaftadine is a H1 histamine receptor antagonist and inhibitor of the release of histamine from mast cells. Decreased chemotaxis and inhibition of eosinophil activation has also been demonstrated.

TargetActionsOrganism
UHistamine H1 receptor
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

The protein binding of alcaftadine and the active metabolite are 39.2% and 62.7% respectively.

Metabolism

The metabolism of alcaftadine is mediated by non-CYP450 cytosolic enzymes to the active carboxylic acid metabolite.

Route of elimination

Based on data following oral administration of alcaftadine, the carboxylic acid metabolite is primarily eliminated unchanged in the urine.

Half life

The elimination half-life of the carboxylic acid metabolite is approximately 2 hours following topical ocular administration.

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

References

General References
  1. Mahvan TD, Buckley WA, Hornecker JR: Alcaftadine for the prevention of itching associated with allergic conjunctivitis. Ann Pharmacother. 2012 Jul-Aug;46(7-8):1025-32. doi: 10.1345/aph.1Q755. Epub 2012 Jul 17. [PubMed:22811343]
  2. Simons FE, Simons KJ: Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol. 2011 Dec;128(6):1139-1150.e4. doi: 10.1016/j.jaci.2011.09.005. Epub 2011 Oct 27. [PubMed:22035879]
  3. Hussar DA, Samuel J: Vilazodone hydrochloride, linagliptin, and alcaftadine. J Am Pharm Assoc (2003). 2011 Jul-Aug;51(4):557-9. doi: 10.1331/JAPhA.2011.11534. [PubMed:21752782]
External Links
Human Metabolome Database
HMDB0015670
KEGG Drug
D06552
PubChem Compound
19371515
PubChem Substance
99443288
ChemSpider
14201635
ChEBI
71023
ChEMBL
CHEMBL1201747
PharmGKB
PA165958399
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Alcaftadine
ATC Codes
S01GX11 — Alcaftadine
FDA label
Download (146 KB)
MSDS
Download (567 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentConjunctivitis, Seasonal Allergic1
4CompletedTreatmentConjunctivitis, Seasonal Allergic3
4Unknown StatusTreatmentConjunctivitis, Seasonal Allergic1
4Unknown StatusTreatmentConjunctivitis, Seasonal Allergic / Rhinoconjunctivitis1
Not AvailableRecruitingNot AvailableConjunctivitis, Seasonal Allergic1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Solution / dropsOphthalmic2.5 mg/mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8664215No2007-12-232027-12-23Us
US5468743No1996-04-202016-04-20Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
boiling point (°C)556.247 °C at 760 mmHg.# http://www.lookchem.com/Product_842767/CasNo_147084-10-4/Alcaftadine.html#.UXtC3Ct5N_k
water solubilityslightly solubilityFDA Label
logP3.202# http://www.lookchem.com/Product_842767/CasNo_147084-10-4/Alcaftadine.html#.UXtC3Ct5N_k
Predicted Properties
PropertyValueSource
Water Solubility0.333 mg/mLALOGPS
logP2.09ALOGPS
logP2.17ChemAxon
logS-3ALOGPS
pKa (Strongest Basic)7.16ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area38.13 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity102.88 m3·mol-1ChemAxon
Polarizability34.68 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9745
Caco-2 permeable+0.5974
P-glycoprotein substrateSubstrate0.8775
P-glycoprotein inhibitor IInhibitor0.8923
P-glycoprotein inhibitor IIInhibitor0.7024
Renal organic cation transporterInhibitor0.7448
CYP450 2C9 substrateNon-substrate0.7517
CYP450 2D6 substrateNon-substrate0.7096
CYP450 3A4 substrateSubstrate0.613
CYP450 1A2 substrateInhibitor0.6525
CYP450 2C9 inhibitorNon-inhibitor0.6685
CYP450 2D6 inhibitorNon-inhibitor0.6573
CYP450 2C19 inhibitorNon-inhibitor0.7002
CYP450 3A4 inhibitorNon-inhibitor0.8498
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6381
Ames testNon AMES toxic0.561
CarcinogenicityNon-carcinogens0.9681
BiodegradationNot ready biodegradable0.969
Rat acute toxicity2.7266 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6292
hERG inhibition (predictor II)Inhibitor0.5603
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 benzazepines. These are organic compounds containing a benzene ring fused to an azepine ring (unsaturated seven-membered heterocycle with one nitrogen atom replacing a carbon atom).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzazepines
Sub Class
Not Available
Direct Parent
Benzazepines
Alternative Parents
Carbonylimidazoles / Azepines / Aryl-aldehydes / Piperidines / N-substituted imidazoles / Benzenoids / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds
show 2 more
Substituents
Benzazepine / Azepine / Imidazole-4-carbonyl group / Aryl-aldehyde / N-substituted imidazole / Piperidine / Benzenoid / Imidazole / Azole / Heteroaromatic compound
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
piperidines, tertiary amino compound, aldehyde, imidazobenzazepine (CHEBI:71023)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Simons FE, Simons KJ: Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol. 2011 Dec;128(6):1139-1150.e4. doi: 10.1016/j.jaci.2011.09.005. Epub 2011 Oct 27. [PubMed:22035879]
  2. LASTACAFT [Link]

Drug created on September 14, 2010 10:21 / Updated on June 02, 2018 07:46