Levocabastine

Synonyms :
Levocabastin, Levocabastina, Levocabastinum

Status : approved

Category

Histamine H1 Antagonists, Non-Sedating

Therapeutic Classification

DECONGESTANTS AND OTHER NASAL PREPARATIONS FOR TOPICAL USE

RESPIRATORY SYSTEM
NASAL PREPARATIONS
DECONGESTANTS AND OTHER NASAL PREPARATIONS FOR TOPICAL USE

Description

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

Used

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.

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.

Dosage

Form Route Strength
Drops; suspension ophthalmic 0.5 mg
Suspension; spray nasal 0.5 mg

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.

Toxic Effect

Adverse effects include visual disturbances, dry mouth, cough, nausea, eyelid edema and lacrimation.

Metabolism

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

Absorption

After instillation in the eye, levocabastine is systemically absorbed, albeit at low levels.

Half Life

36 hours (after oral administration)

Chemical Classification

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.

Phenylpiperidines

Organic compounds

Organoheterocyclic compounds

Piperidines

Phenylpiperidines

Chemical Name

Levocabastin

Brands

name Dosage form Country
Livostin Eye Drops drops; suspension Canada
Livostin Sus Nas 0.5mg/ml suspension; spray Canada

Drug Drug Interactions

  •  Aclidinium  : May enhance the anticholinergic effect of Anticholinergic Agents.
  •  Botulinum Toxin Type A  : Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA.
  •  Botulinum Toxin Type A  : Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA.
  •  Botulinum Toxin Type B  : Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB.
  •  Buprenorphine  : CNS Depressants may enhance the CNS depressant effect of Buprenorphine.
  •  Doxylamine  : May enhance the CNS depressant effect of CNS Depressants.
  •  Dronabinol  : May enhance the CNS depressant effect of CNS Depressants.
  •  Dronabinol  : May enhance the CNS depressant effect of CNS Depressants.
  •  Glucagon recombinant  : Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased.
  •  Hyaluronidase  : Antihistamines may diminish the therapeutic effect of Hyaluronidase.
  •  Hydrocodone  : CNS Depressants may enhance the CNS depressant effect of Hydrocodone.
  •  Hydroxyzine  : May enhance the CNS depressant effect of CNS Depressants.
  •  Itopride  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Magnesium Sulfate  : May enhance the CNS depressant effect of CNS Depressants.
  •  Metyrosine  : CNS Depressants may enhance the sedative effect of Metyrosine.
  •  Mianserin  : May enhance the anticholinergic effect of Anticholinergic Agents.
  •  Minocycline  : May enhance the CNS depressant effect of CNS Depressants.
  •  Mirabegron  : Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron.
  •  Mirtazapine  : CNS Depressants may enhance the CNS depressant effect of Mirtazapine.
  •  Nabilone  : May enhance the CNS depressant effect of CNS Depressants.
  •  Orphenadrine  : CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
  •  Paraldehyde  : CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
  •  Perampanel  : May enhance the CNS depressant effect of CNS Depressants.
  •  Potassium Chloride  : Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride.
  •  Pramipexole  : CNS Depressants may enhance the sedative effect of Pramipexole.
  •  Ropinirole  : CNS Depressants may enhance the sedative effect of Ropinirole.
  •  Rotigotine  : CNS Depressants may enhance the sedative effect of Rotigotine.
  •  Rufinamide  : May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.
  •  Secretin  : Anticholinergic Agents may diminish the therapeutic effect of Secretin.
  •  Sodium oxybate  : May enhance the CNS depressant effect of CNS Depressants.
  •  Sulpiride  : Anticholinergic Agents may diminish the therapeutic effect of LevoSulpiride.
  •  Suvorexant  : CNS Depressants may enhance the CNS depressant effect of Suvorexant.
  •  Tapentadol  : May enhance the CNS depressant effect of CNS Depressants.
  •  Thalidomide  : CNS Depressants may enhance the CNS depressant effect of Thalidomide.
  •  Tiotropium  : Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium.
  •  Topiramate  : Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate.
  •  Umeclidinium  : May enhance the anticholinergic effect of Anticholinergic Agents.
  •  Zolpidem  : CNS Depressants may enhance the CNS depressant effect of Zolpidem.

Calculated Property

kind Value Source
logP 4.56 ALOGPS
logS -5.1 ALOGPS
Water Solubility 3.47e-03 g/l ALOGPS
logP 2.5 ChemAxon
IUPAC Name (3S,4R)-1-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-3-methyl-4-phenylpiperidine-4-carboxylic acid ChemAxon
Traditional IUPAC Name livostin ChemAxon
Molecular Weight 420.5191 ChemAxon
Monoisotopic Weight 420.221306387 ChemAxon
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 ChemAxon
Molecular Formula C26H29FN2O2 ChemAxon
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 ChemAxon
InChIKey InChIKey=ZCGOMHNNNFPNMX-YHYDXASRSA-N ChemAxon
Polar Surface Area (PSA) 64.33 ChemAxon
Refractivity 118.48 ChemAxon
Polarizability 45.72 ChemAxon
Rotatable Bond Count 4 ChemAxon
H Bond Acceptor Count 4 ChemAxon
H Bond Donor Count 1 ChemAxon
pKa (strongest acidic) 3.71 ChemAxon
pKa (strongest basic) 10.32 ChemAxon
Physiological Charge 0 ChemAxon
Number of Rings 4 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 1 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Histamine H1 receptor : in Human
  • Neurotensin receptor type 2 : in Human