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Identification
NameLevocabastine
Accession NumberDB01106  (APRD01069)
TypeSmall Molecule
GroupsApproved
Description

Levocabastine is a selective second-generation H1-receptor antagonist used for allergic conjunctivitis. Levocabastine was discovered at Janssen Pharmaceutica in 1979.

Structure
Thumb
Synonyms
SynonymLanguageCode
LevocabastinNot AvailableNot Available
LevocabastinaSpanishNot Available
LevocabastinumLatinNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
LivostinNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number79516-68-0
WeightAverage: 420.5191
Monoisotopic: 420.221306387
Chemical FormulaC26H29FN2O2
InChI KeyZCGOMHNNNFPNMX-YHYDXASRSA-N
InChI
InChI=1S/C26H29FN2O2/c1-19-17-29(16-15-26(19,24(30)31)21-5-3-2-4-6-21)23-11-13-25(18-28,14-12-23)20-7-9-22(27)10-8-20/h2-10,19,23H,11-17H2,1H3,(H,30,31)/t19-,23?,25?,26-/m1/s1
IUPAC Name
(3S,4R)-1-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-3-methyl-4-phenylpiperidine-4-carboxylic acid
SMILES
C[C@@H]1CN(CC[C@]1(C(O)=O)C1=CC=CC=C1)C1CCC(CC1)(C#N)C1=CC=C(F)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpiperidines. These are compounds containing a phenylpiperidine skeleton, which consists of a piperidine bound to a phenyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPiperidines
Sub ClassPhenylpiperidines
Direct ParentPhenylpiperidines
Alternative Parents
Substituents
  • Phenylpiperidine
  • Phenylacetate
  • Piperidinecarboxylic acid
  • Benzyl-cyanide
  • Aralkylamine
  • Halobenzene
  • Fluorobenzene
  • Cyclohexylamine
  • Benzenoid
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl fluoride
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Nitrile
  • Carbonitrile
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationAs an ophthalmic for the temporary relief of the signs and symptoms of seasonal allergic conjunctivitis. Also used as a nasal spray for allergic rhinitis.
PharmacodynamicsLevocabastine is a selective histamine H1-receptor antagonist exerting inhibitory effects on the release of chemical mediators from mast cells and on the chemotaxis of polymorphonuclear leukocytes and eosinophils. Both histamine and antigens induced conjunctivitis can be inhibited by levocabastine. Levocabastine can also reduce symptoms of allergic rhinitis by preventing an increase in vascular permeability of nasal mucosa.
Mechanism of actionLevocabastine is a potent, selective histamine H1-receptor antagonist. It works by competing with histamine for H1-receptor sites on effector cells. It thereby prevents, but does not reverse, responses mediated by histamine alone. Levocabastine does not block histamine release but, rather, prevents histamine binding and activity. Levocabastine also binds neurotensin 2 receptors and serves as a neurotensin agonist. This can induce some degree of analgesia.
AbsorptionAfter instillation in the eye, levocabastine is systemically absorbed, albeit at low levels.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Mostly unchanged. 10 to 20% is metabolized to the acylglucuronide of levocabastine.

Route of eliminationNot Available
Half life36 hours (after oral administration)
ClearanceNot Available
ToxicityAdverse effects include visual disturbances, dry mouth, cough, nausea, eyelid edema and lacrimation.
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+0.9811
Blood Brain Barrier+0.8388
Caco-2 permeable+0.5747
P-glycoprotein substrateSubstrate0.7325
P-glycoprotein inhibitor IInhibitor0.5
P-glycoprotein inhibitor IINon-inhibitor0.5682
Renal organic cation transporterNon-inhibitor0.5526
CYP450 2C9 substrateNon-substrate0.7708
CYP450 2D6 substrateNon-substrate0.6679
CYP450 3A4 substrateSubstrate0.5153
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 substrateNon-inhibitor0.9071
CYP450 2D6 substrateInhibitor0.8932
CYP450 2C19 substrateNon-inhibitor0.9026
CYP450 3A4 substrateNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9046
Ames testNon AMES toxic0.7503
CarcinogenicityNon-carcinogens0.9196
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.9608 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9404
hERG inhibition (predictor II)Inhibitor0.625
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubility>0.5 mg/mLNot Available
logP5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00347 mg/mLALOGPS
logP4.56ALOGPS
logP2.5ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)3.71ChemAxon
pKa (Strongest Basic)10.32ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area64.33 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity118.48 m3·mol-1ChemAxon
Polarizability45.72 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ATC CodesR01AC02S01GX02
AHFS Codes
  • 52:02.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. Neurotensin receptor type 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: partial antagonist

Components

Name UniProt ID Details
Neurotensin receptor type 2 O95665 Details

References:

  1. Richard F, Barroso S, Martinez J, Labbe-Jullie C, Kitabgi P: Agonism, inverse agonism, and neutral antagonism at the constitutively active human neurotensin receptor 2. Mol Pharmacol. 2001 Dec;60(6):1392-8. Pubmed
  2. Chalon P, Vita N, Kaghad M, Guillemot M, Bonnin J, Delpech B, Le Fur G, Ferrara P, Caput D: Molecular cloning of a levocabastine-sensitive neurotensin binding site. FEBS Lett. 1996 May 20;386(2-3):91-4. Pubmed
  3. Botto JM, Guillemare E, Vincent JP, Mazella J: Effects of SR 48692 on neurotensin-induced calcium-activated chloride currents in the Xenopus oocyte expression system: agonist-like activity on the levocabastine-sensitive neurotensin receptor and absence of antagonist effect on the levocabastine insensitive neurotensin receptor. Neurosci Lett. 1997 Feb 28;223(3):193-6. Pubmed

2. Histamine H1 receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Histamine H1 receptor P35367 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Sugimoto Y, Iba Y, Ishizawa K, Suzuki G, Kamei C: Effects of levocabastine on lipid mediator release from guinea pig lung fragments. Acta Med Okayama. 1999 Dec;53(6):271-4. Pubmed
  3. Chalon P, Vita N, Kaghad M, Guillemot M, Bonnin J, Delpech B, Le Fur G, Ferrara P, Caput D: Molecular cloning of a levocabastine-sensitive neurotensin binding site. FEBS Lett. 1996 May 20;386(2-3):91-4. Pubmed
  4. Yamada M, Yamada M, Lombet A, Forgez P, Rostene W: Distinct functional characteristics of levocabastine sensitive rat neurotensin NT2 receptor expressed in Chinese hamster ovary cells. Life Sci. 1998;62(23):PL 375-80. Pubmed
  5. Betancur C, Canton M, Burgos A, Labeeuw B, Gully D, Rostene W, Pelaprat D: Characterization of binding sites of a new neurotensin receptor antagonist, [3H]SR 142948A, in the rat brain. Eur J Pharmacol. 1998 Feb 5;343(1):67-77. Pubmed
  6. Akiyoshi M, Shigeoka T, Torii S, Maki E, Enomoto S, Takahashi H, Hirano F: [Pharmacological and clinical properties of levocabastine hydrochloride (eye drop and nasal spray), a selective H1 antagonist] Nippon Yakurigaku Zasshi. 2002 Mar;119(3):175-84. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13