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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyLevocabastine
Identification
- Name
- Levocabastine
- Accession Number
- DB01106 (APRD01069)
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Description
Levocabastine is a selective second-generation H1-receptor antagonist used for allergic conjunctivitis. Levocabastine was discovered at Janssen Pharmaceutica in 1979.
- Structure
Structure for Levocabastine (DB01106)
- Synonyms
- Levocabastin
- Levocabastina
- Levocabastinum
- Product Ingredients
Ingredient UNII CAS InChI Key Levocabastine hydrochloride 124XMA6YEI 79547-78-7 OICFWWJHIMKBCD-VALQNVSPSA-N - Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Livostin Suspension 0.5 mg/1mL Ophthalmic Physicians Total Care, Inc. 2004-04-28 2006-06-30 US 
Livostin Suspension 0.5 mg/1mL Ophthalmic Novartis Ophthalmics 2006-01-12 Not applicable US Livostin Eye Drops Solution / drops; Suspension 0.5 mg Ophthalmic Novartis 1995-12-31 2011-06-27 Canada 
Livostin Sus Nas 0.5mg/ml Spray; Suspension 0.5 mg Nasal Janssen Pharmaceuticals 1993-12-31 Not applicable Canada - International/Other Brands
- Livostin
- Categories
- Anti-Allergic Agents
- Antiallergic Agents, Excl. Corticosteroids
- Central Nervous System Depressants
- Decongestants and Antiallergics
- Histamine Agents
- Histamine Antagonists
- Histamine H1 Antagonists
- Histamine H1 Antagonists, Non-Sedating
- Nasal Preparations
- Neurotransmitter Agents
- Ophthalmologicals
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- Sensory Organs
- UNII
- H68BP06S81
- CAS number
- 79516-68-0
- Weight
- Average: 420.528
Monoisotopic: 420.221306345 - Chemical Formula
- C26H29FN2O2
- InChI Key
- ZCGOMHNNNFPNMX-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)[C@H]1CC[C@](CC1)(C#N)C1=CC=C(F)C=C1
Pharmacology
- Indication
As an ophthalmic for the temporary relief of the signs and symptoms of seasonal allergic conjunctivitis. Also used as a nasal spray for allergic rhinitis.
- Associated Conditions
- Pharmacodynamics
Levocabastine 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 action
Levocabastine 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.
Target Actions Organism AHistamine H1 receptor antagonistHuman ANeurotensin receptor type 2 partial antagonistHuman - Absorption
After instillation in the eye, levocabastine is systemically absorbed, albeit at low levels.
- Volume of distribution
- Not Available
- Protein binding
- Not Available
- Metabolism
Mostly unchanged. 10 to 20% is metabolized to the acylglucuronide of levocabastine.
- Route of elimination
- Not Available
- Half life
36 hours (after oral administration)
- Clearance
- Not Available
- Toxicity
Adverse effects include visual disturbances, dry mouth, cough, nausea, eyelid edema and lacrimation.
- Affected organisms
- Humans and other mammals
- Pathways
Pathway Category Levocabastine H1-Antihistamine Action Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction Azelastine Levocabastine may increase the central nervous system depressant (CNS depressant) activities of Azelastine. - Food Interactions
- Not Available
References
- General References
- Not Available
- External Links
- KEGG Drug
- D01717
- PubChem Compound
- 54385
- PubChem Substance
- 46505909
- ChemSpider
- 16736421
- BindingDB
- 50019405
- ChEBI
- 135679
- ChEMBL
- CHEMBL1615438
- Therapeutic Targets Database
- DAP000335
- PharmGKB
- PA164742988
- IUPHAR
- 1586
- Guide to Pharmacology
- GtP Drug Page
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Levocabastine
- ATC Codes
- R01AC02 — Levocabastine
- R01AC — Antiallergic agents, excl. corticosteroids
- R01A — DECONGESTANTS AND OTHER NASAL PREPARATIONS FOR TOPICAL USE
- R01 — NASAL PREPARATIONS
- R — RESPIRATORY SYSTEM
- AHFS Codes
- 52:02.00 — Antiallergic Agents
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment Rhinitis, Allergic, Perennial and Seasonal 2 3 Completed Treatment Rhinitis, Allergic, Perennial 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Novartis AG
- OMJ Pharmaceuticals
- Physicians Total Care Inc.
- Dosage forms
Form Route Strength Suspension Ophthalmic 0.5 mg/1mL Solution / drops; suspension Ophthalmic 0.5 mg Spray; suspension Nasal 0.5 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility >0.5 mg/mL Not Available logP 5 Not Available - Predicted Properties
Property Value Source Water Solubility 0.00347 mg/mL ALOGPS logP 4.56 ALOGPS logP 2.5 ChemAxon logS -5.1 ALOGPS pKa (Strongest Acidic) 3.71 ChemAxon pKa (Strongest Basic) 10.32 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 4 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 64.33 Å2 ChemAxon Rotatable Bond Count 4 ChemAxon Refractivity 118.48 m3·mol-1 ChemAxon Polarizability 45.58 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.9811 Blood Brain Barrier + 0.8388 Caco-2 permeable + 0.5747 P-glycoprotein substrate Substrate 0.7325 P-glycoprotein inhibitor I Inhibitor 0.5 P-glycoprotein inhibitor II Non-inhibitor 0.5682 Renal organic cation transporter Non-inhibitor 0.5526 CYP450 2C9 substrate Non-substrate 0.7708 CYP450 2D6 substrate Non-substrate 0.6679 CYP450 3A4 substrate Substrate 0.5153 CYP450 1A2 substrate Non-inhibitor 0.9046 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Inhibitor 0.8932 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9046 Ames test Non AMES toxic 0.7503 Carcinogenicity Non-carcinogens 0.9196 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.9608 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9404 hERG inhibition (predictor II) Inhibitor 0.625
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Taxonomy
- Description
- This 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.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Piperidines
- Sub Class
- Phenylpiperidines
- Direct Parent
- Phenylpiperidines
- Alternative Parents
- Piperidinecarboxylic acids / Aralkylamines / Fluorobenzenes / Cyclohexylamines / Aryl fluorides / Trialkylamines / Amino acids / Nitriles / Monocarboxylic acids and derivatives / Azacyclic compounds show 6 more
- Substituents
- Phenylpiperidine / Piperidinecarboxylic acid / Cyclohexylamine / Fluorobenzene / Aralkylamine / Halobenzene / Aryl fluoride / Aryl halide / Monocyclic benzene moiety / Benzenoid show 22 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
Targets
- 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
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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
- Uniprot Name
- Neurotensin receptor type 2
- Molecular Weight
- 45384.635 Da
References
- 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]
- 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]
- 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]
Drug created on June 13, 2005 07:24 / Updated on November 13, 2018 07:56