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

Structure

Similar Structures

Synonyms

Levocabastina
Levocabastine
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
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Livostin	Suspension	0.5 mg/1mL	Ophthalmic	Physicians Total Care, Inc.	2004-04-28	2006-06-30
Livostin	Suspension	0.5 mg/1mL	Ophthalmic	Novartis Ophthalmics	2006-01-12	Not applicable
Livostin Eye Drops	Solution / drops; Suspension		Ophthalmic	Novartis	1995-12-31	2011-06-27
Livostin Sus Nas 0.5mg/ml	Spray; Suspension		Nasal	Janssen Pharmaceuticals	1993-12-31	Not applicable

Additional Data Available

Application Number

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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Product Code

A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

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

Allergic Rhinitis (AR)

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	antagonist	Humans
ANeurotensin receptor type 2	partial antagonist	Humans

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Additional Data Available

Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available

Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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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

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Abexinostat	The risk or severity of QTc prolongation can be increased when Levocabastine is combined with Abexinostat.
Acebutolol	The risk or severity of QTc prolongation can be increased when Levocabastine is combined with Acebutolol.
Aceprometazine	The risk or severity of QTc prolongation can be increased when Levocabastine is combined with Aceprometazine.
Acetyldigoxin	The risk or severity of QTc prolongation can be increased when Levocabastine is combined with Acetyldigoxin.
Aclidinium	Levocabastine may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
Acrivastine	The risk or severity of QTc prolongation can be increased when Levocabastine is combined with Acrivastine.
Adenosine	The risk or severity of QTc prolongation can be increased when Levocabastine is combined with Adenosine.
Ajmaline	The risk or severity of QTc prolongation can be increased when Levocabastine is combined with Ajmaline.
Ajulemic acid	The risk or severity of adverse effects can be increased when Ajulemic acid is combined with Levocabastine.
Alaproclate	The risk or severity of adverse effects can be increased when Levocabastine is combined with Alaproclate.

Additional Data Available

Extended Description

Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

A severity rating for each drug interaction, from minor to major.

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Evidence Level

A rating for the strength of the evidence supporting each drug interaction.

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Action

An effect category for each drug interaction. Know how this interaction affects the subject drug.

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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
Guide to Pharmacology: GtP Drug Page
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Levocabastine

ATC Codes

R01AC02 — Levocabastine

S01GX02 — Levocabastine

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
Not Available	Recruiting	Treatment	Determination of the Efficacy of Different Medications for Idiopathic Rhinitis / Impact of Different Medications on Biomarkers of Idiopathic Rhinitis / Safety and Tolerance of Different Medications for Idiopathic Rhinitis	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
Spray; 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	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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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

Details1. Histamine H1 receptor

Kind: Protein
Organism: Humans
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]

Details2. Neurotensin receptor type 2

Kind: Protein
Organism: Humans
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 January 27, 2020 23:59

Levocabastine

Identification

Structure for Levocabastine (DB01106)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References