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Identification
Name Levocabastine
Accession Number DB01106 (APRD01069)
Type small molecule
Groups approved
Description

Levocabastine is a selective second-generation H1-receptor antagonist used for allergic conjunctivitis. Levocabastine was discovered at Janssen Pharmaceutica in 1979.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Levocabastin
Levocabastina [Spanish]
Levocabastinum [Latin]
Salts Not Available
Brand names
Name Company
Livostin
Brand mixtures Not Available
Categories
  • Histamine H1 Antagonists
  • Histamine H1 Antagonists, Non-Sedating
CAS number 79516-68-0
Weight Average: 420.5191
Monoisotopic: 420.221306387
Chemical Formula C26H29FN2O2
InChI Key InChIKey=ZCGOMHNNNFPNMX-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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylpiperidines
Substructures
  • Carbonyl Compounds
  • Hydroxy Compounds
  • Acetates
  • Carboxylic Acids and Derivatives
  • Phenylacetates
  • Nitriles and Derivatives
  • Benzene and Derivatives
  • Phenylpiperidines
  • Cyanides
  • Aliphatic and Aryl Amines
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Phenylpropylamines
  • Aryl Halides
  • Piperidines
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.
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.
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 Not Available
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
Packagers
Dosage forms
Form Route Strength
Solution / drops Ophthalmic
Suspension Nasal
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 3.47e-03 g/l 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 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 118.48 ChemAxon
polarizability 45.72 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D01717 Link_out
PubChem Compound 54385 Link_out
PubChem Substance 46505909 Link_out
ChemSpider 49123 Link_out
Therapeutic Targets Database DAP000335 Link_out
PharmGKB PA164742988 Link_out
IUPHAR 1586 Link_out
Guide to Pharmacology 1586 Link_out
Drug Product Database 2131625 Link_out
RxList http://www.rxlist.com/cgi/generic2/livostin.htm Link_out
Drugs.com http://www.drugs.com/mtm/levocabastine-ophthalmic.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Levocabastine Link_out
ATC Codes
  • R01AC02
  • S01GX02
AHFS Codes
  • 52:02.00
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Searched, but no interactions found.
Food Interactions Not Available
Targets

1. Histamine H1 receptor

Pharmacological action: yes
Actions: antagonist

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

Organism class: human
UniProt ID: P35367 Link_out
Gene: HRH1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

2. Neurotensin receptor type 2

Pharmacological action: yes
Actions: partial antagonist

Receptor for the tridecapeptide neurotensin. It is associated with G proteins that activate a phosphatidylinositol- calcium second messenger system

Organism class: human
UniProt ID: O95665 Link_out
Gene: NTSR2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19