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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
Levocabastin
Levocabastina
Levocabastinum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Livostin Eye Dropsdrops; suspension0.5 mgophthalmicNovartis Pharmaceuticals Canada Inc1995-12-312011-06-27Canada
Livostin Sus Nas 0.5mg/mlsuspension; spray0.5 mgnasalJanssen Inc1993-12-31Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
LivostinNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Levocabastine hydrochloride
79547-78-7
Thumb
  • InChI Key: OICFWWJHIMKBCD-VALQNVSPSA-N
  • Monoisotopic Mass: 456.1979841
  • Average Mass: 456.99
DBSALT001442
Categories
UNIIH68BP06S81
CAS number79516-68-0
WeightAverage: 420.528
Monoisotopic: 420.221306345
Chemical FormulaC26H29FN2O2
InChI KeyZCGOMHNNNFPNMX-KYTRFIICSA-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)-3-methyl-4-phenyl-1-[(1s,4s)-4-cyano-4-(4-fluorophenyl)cyclohexyl]piperidine-4-carboxylic acid
SMILES
C[C@@H]1CN(CC[C@]1(C(O)=O)C1=CC=CC=C1)[[email protected]]1CC[C@](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
  • Piperidinecarboxylic acid
  • Cyclohexylamine
  • Fluorobenzene
  • Aralkylamine
  • Halobenzene
  • Aryl fluoride
  • Aryl halide
  • Monocyclic benzene moiety
  • Benzenoid
  • Amino acid or derivatives
  • Amino acid
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid derivative
  • Carboxylic acid
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carbonitrile
  • Nitrile
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Amine
  • Carbonyl group
  • Organic oxygen compound
  • Cyanide
  • Organic oxide
  • Organohalogen compound
  • Organofluoride
  • Organonitrogen compound
  • 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.
Related Articles
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 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Drops; suspensionophthalmic0.5 mg
Suspension; spraynasal0.5 mg
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
Polarizability45.58 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 ReferencesNot Available
External Links
ATC CodesR01AC02S01GX02
AHFS Codes
  • 52:02.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AclidiniumAclidinium may increase the anticholinergic activities of Levocabastine.
AzelastineLevocabastine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
Botulinum Toxin Type ALevocabastine may increase the anticholinergic activities of Botulinum Toxin Type A.
Botulinum Toxin Type BLevocabastine may increase the anticholinergic activities of Botulinum Toxin Type B.
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Levocabastine.
BuprenorphineLevocabastine may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
CimetropiumLevocabastine may increase the anticholinergic activities of Cimetropium Bromide.
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Levocabastine.
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Levocabastine.
EluxadolineLevocabastine may increase the activities of Eluxadoline.
Glucagon recombinantThe risk or severity of adverse effects can be increased when Levocabastine is combined with Glucagon recombinant.
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Levocabastine.
HydrocodoneLevocabastine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Levocabastine.
Ipratropium bromideIpratropium bromide may increase the anticholinergic activities of Levocabastine.
ItoprideThe therapeutic efficacy of Itopride can be decreased when used in combination with Levocabastine.
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Levocabastine.
MetyrosineLevocabastine may increase the sedative activities of Metyrosine.
MianserinMianserin may increase the anticholinergic activities of Levocabastine.
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Levocabastine.
MirabegronThe risk or severity of adverse effects can be increased when Levocabastine is combined with Mirabegron.
MirtazapineLevocabastine may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
MorphineThe risk or severity of adverse effects can be increased when Levocabastine is combined with Morphine.
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Levocabastine.
OrphenadrineLevocabastine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
ParaldehydeLevocabastine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
ParoxetineThe risk or severity of adverse effects can be increased when Levocabastine is combined with Paroxetine.
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Levocabastine.
Potassium ChlorideLevocabastine may increase the ulcerogenic activities of Potassium Chloride.
PramipexoleLevocabastine may increase the sedative activities of Pramipexole.
RamosetronLevocabastine may increase the activities of Ramosetron.
RopiniroleLevocabastine may increase the sedative activities of Ropinirole.
RotigotineLevocabastine may increase the sedative activities of Rotigotine.
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Levocabastine.
SecretinThe therapeutic efficacy of Secretin can be decreased when used in combination with Levocabastine.
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Levocabastine.
SulpirideThe therapeutic efficacy of Sulpiride can be decreased when used in combination with Levocabastine.
SuvorexantLevocabastine may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
TacrineThe therapeutic efficacy of Levocabastine can be decreased when used in combination with Tacrine.
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Levocabastine.
ThalidomideLevocabastine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
TiotropiumLevocabastine may increase the anticholinergic activities of Tiotropium.
TopiramateThe risk or severity of adverse effects can be increased when Levocabastine is combined with Topiramate.
TrichlormethiazideThe serum concentration of Trichlormethiazide can be increased when it is combined with Levocabastine.
UmeclidiniumUmeclidinium may increase the anticholinergic activities of Levocabastine.
ZolpidemLevocabastine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
partial antagonist
General Function:
G-protein coupled receptor activity
Specific Function:
Receptor for the tridecapeptide neurotensin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Gene Name:
NTSR2
Uniprot ID:
O95665
Molecular Weight:
45384.635 Da
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:11723247 ]
  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:8647296 ]
  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:9080465 ]
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 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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  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:10631382 ]
  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:8647296 ]
  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:9627096 ]
  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:9551716 ]
  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]. Nihon Yakurigaku Zasshi. 2002 Mar;119(3):175-84. [PubMed:11915520 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23