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Identification
NameAlcaftadine
Accession NumberDB06766
TypeSmall Molecule
GroupsApproved
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
Lastacaft
Vilasta
External Identifiers
  • R 89674
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Lastacaftsolution/ drops2.5 mg/mLophthalmicAllergan, Inc.2010-11-01Not applicableUs
Lastacaftsolution/ drops2.5 mg/mLophthalmicPhysicians Total Care, Inc.2011-08-19Not applicableUs
Lastacaftsolution/ drops2.5 mg/mLophthalmicRebel Distributors Corp2010-11-01Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII7Z8O94ECSX
CAS number147084-10-4
WeightAverage: 307.3895
Monoisotopic: 307.168462309
Chemical FormulaC19H21N3O
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzazepines
Sub ClassNot Available
Direct ParentBenzazepines
Alternative Parents
Substituents
  • Benzazepine
  • Aryl-aldehyde
  • Azepine
  • Benzenoid
  • Piperidine
  • N-substituted imidazole
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aldehyde
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the prevention of itching associated with allergic conjunctivitis.
PharmacodynamicsFollowing 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 actionAlcaftadine 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingThe 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 eliminationBased on data following oral administration of alcaftadine, the carboxylic acid metabolite is primarily eliminated unchanged in the urine.
Half lifeThe elimination half-life of the carboxylic acid metabolite is approximately 2 hours following topical ocular administration.
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Solution/ dropsophthalmic2.5 mg/mL
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5468743 No1996-04-202016-04-20Us
US8664215 No2007-12-232027-12-23Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
boiling point556.247 °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 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 ReferenceNot Available
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
ATC CodesS01GX11
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (146 KB)
MSDSDownload (567 KB)
Interactions
Drug Interactions
Drug
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Alcaftadine.
3,4-Methylenedioxymethamphetamine3,4-Methylenedioxymethamphetamine may decrease the sedative activities of Alcaftadine.
AmphetamineAmphetamine may decrease the sedative activities of Alcaftadine.
BenzphetamineBenzphetamine may decrease the sedative activities of Alcaftadine.
Benzylpenicilloyl PolylysineAlcaftadine may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Alcaftadine.
ChlorphentermineChlorphentermine may decrease the sedative activities of Alcaftadine.
DextroamphetamineDextroamphetamine may decrease the sedative activities of Alcaftadine.
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Alcaftadine.
Hydroxyamphetamine hydrobromideHydroxyamphetamine hydrobromide may decrease the sedative activities of Alcaftadine.
LisdexamfetamineLisdexamfetamine may decrease the sedative activities of Alcaftadine.
MephentermineMephentermine may decrease the sedative activities of Alcaftadine.
MethamphetamineMethamphetamine may decrease the sedative activities of Alcaftadine.
PhenterminePhentermine may decrease the sedative activities of Alcaftadine.
Food InteractionsNot Available

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 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. 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]
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Drug created on September 14, 2010 10:21 / Updated on August 30, 2016 02:11