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Details

Stereochemistry ABSOLUTE
Molecular Formula C26H29FN2O2
Molecular Weight 420.5191
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LEVOCABASTINE

SMILES

C[C@@H]1CN(CC[C@]1(C(O)=O)C2=CC=CC=C2)[C@H]3CC[C@](CC3)(C#N)C4=CC=C(F)C=C4

InChI

InChIKey=ZCGOMHNNNFPNMX-KYTRFIICSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including http://www.rxlist.com/livostin-side-effects-drug-center.htm

Levocabastine (trade name Livo) is a selective second-generation H1-receptor antagonist used for allergic conjunctivitis. Levocabastine binds the G protein-coupled neurotensin receptor 2 (NTR2), but not NTR1, where it behaves as a weak partial inverse agonist. In an environmental study, LIVOSTIN 0.05% (levocabastine hydrochloride ophthalmic suspension) instilled four times daily was shown to be significantly more effective than its vehicle in reducing ocular itching associated with seasonal allergic conjunctivitis. After instillation in the eye, levocabastine is systemically absorbed. However, the amount of systemically absorbed levocabastine after therapeutic ocular doses is low (mean plasma concentrations in the range of 1-2 ng/mL). Brand name Livostin is no longer available in the U.S., but generic versions may still be available. Common side effects include burning, stinging, itching, or watering of the eyes, eye irritation or discomfort, blurred vision, dry or puffy eyes, headache, nosebleed, nausea, or fatigue.

Originator

Curator's Comment: # Janssen Pharmaceutical

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: O95665
Gene ID: 23620.0
Gene Symbol: NTSR2
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
LIVOSTIN

Approved Use

LIVOSTIN™ 0.05% (levocabastine hydrochloride ophthalmic suspension) is indicated for the temporary relief of the signs and symptoms of seasonal allergic conjunctivitis.

Launch Date

7.5288963E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
7.4 ng/mL
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOCABASTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
22.2 μg/L
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOCABASTINE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
7.3 μg/L
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOCABASTINE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
12.1 μg/L
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOCABASTINE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
319 ng × h/mL
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOCABASTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
1142 μg × h/L
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOCABASTINE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
337 μg × h/L
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOCABASTINE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
580 μg × h/L
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOCABASTINE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
35.7 h
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOCABASTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
37.5 h
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOCABASTINE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
37.5 h
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOCABASTINE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
45%
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOCABASTINE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
45%
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOCABASTINE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
45%
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEVOCABASTINE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
0.05 % 4 times / day multiple, ophthalmic
Recommended
Dose: 0.05 %, 4 times / day
Route: ophthalmic
Route: multiple
Dose: 0.05 %, 4 times / day
Sources: Page: 12
unhealthy, 5 - 17 years
n = 24
Health Status: unhealthy
Condition: paralimbic keratitis of immuno-allergic type
Age Group: 5 - 17 years
Sex: M+F
Population Size: 24
Sources: Page: 12
Disc. AE: Headache, Blepharoconjunctivitis...
AEs leading to
discontinuation/dose reduction:
Headache (3 patients)
Blepharoconjunctivitis (3 patients)
Sources: Page: 12
0.5 mg/mL 2 times / day multiple, ophthalmic
Recommended
Dose: 0.5 mg/mL, 2 times / day
Route: ophthalmic
Route: multiple
Dose: 0.5 mg/mL, 2 times / day
Co-administed with::
sodium cromoglycate nasal spray(20 mg/ml)
Sources:
unhealthy, < 12 years
n = 177
Health Status: unhealthy
Condition: allergic conjunctivitis
Age Group: < 12 years
Sex: M+F
Population Size: 177
Sources:
Other AEs: Eye disorders NEC...
0.5 mg/mL 2 times / day multiple, ophthalmic
Recommended
Dose: 0.5 mg/mL, 2 times / day
Route: ophthalmic
Route: multiple
Dose: 0.5 mg/mL, 2 times / day
Co-administed with::
sodium cromoglycate nasal spray(20 mg/ml)
Sources:
unhealthy, > 12 years
n = 56
Health Status: unhealthy
Condition: allergic conjunctivitis
Age Group: > 12 years
Sex: M+F
Population Size: 56
Sources:
Other AEs: Eye disorders NEC...
0.05 % 4 times / day multiple, ophthalmic
Recommended
Dose: 0.05 %, 4 times / day
Route: ophthalmic
Route: multiple
Dose: 0.05 %, 4 times / day
Sources: Page: 11
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: allergic conjunctivitis
Age Group: adult
Sex: unknown
Population Size: 148
Sources: Page: 11
Disc. AE: Eye disorders NEC...
AEs leading to
discontinuation/dose reduction:
Eye disorders NEC (23 patients)
Sources: Page: 11
0.2 mg/mL 2 times / day multiple, intranasal
Recommended
Dose: 0.2 mg/mL, 2 times / day
Route: intranasal
Route: multiple
Dose: 0.2 mg/mL, 2 times / day
Sources:
unhealthy, mean 38.8 years
n = 137
Health Status: unhealthy
Condition: seasonal allergic rhinitis
Age Group: mean 38.8 years
Sex: M+F
Population Size: 137
Sources:
AEs

AEs

AESignificanceDosePopulation
Blepharoconjunctivitis 3 patients
Disc. AE
0.05 % 4 times / day multiple, ophthalmic
Recommended
Dose: 0.05 %, 4 times / day
Route: ophthalmic
Route: multiple
Dose: 0.05 %, 4 times / day
Sources: Page: 12
unhealthy, 5 - 17 years
n = 24
Health Status: unhealthy
Condition: paralimbic keratitis of immuno-allergic type
Age Group: 5 - 17 years
Sex: M+F
Population Size: 24
Sources: Page: 12
Headache 3 patients
Disc. AE
0.05 % 4 times / day multiple, ophthalmic
Recommended
Dose: 0.05 %, 4 times / day
Route: ophthalmic
Route: multiple
Dose: 0.05 %, 4 times / day
Sources: Page: 12
unhealthy, 5 - 17 years
n = 24
Health Status: unhealthy
Condition: paralimbic keratitis of immuno-allergic type
Age Group: 5 - 17 years
Sex: M+F
Population Size: 24
Sources: Page: 12
Eye disorders NEC 33 patients
0.5 mg/mL 2 times / day multiple, ophthalmic
Recommended
Dose: 0.5 mg/mL, 2 times / day
Route: ophthalmic
Route: multiple
Dose: 0.5 mg/mL, 2 times / day
Co-administed with::
sodium cromoglycate nasal spray(20 mg/ml)
Sources:
unhealthy, < 12 years
n = 177
Health Status: unhealthy
Condition: allergic conjunctivitis
Age Group: < 12 years
Sex: M+F
Population Size: 177
Sources:
Eye disorders NEC 7 patients
0.5 mg/mL 2 times / day multiple, ophthalmic
Recommended
Dose: 0.5 mg/mL, 2 times / day
Route: ophthalmic
Route: multiple
Dose: 0.5 mg/mL, 2 times / day
Co-administed with::
sodium cromoglycate nasal spray(20 mg/ml)
Sources:
unhealthy, > 12 years
n = 56
Health Status: unhealthy
Condition: allergic conjunctivitis
Age Group: > 12 years
Sex: M+F
Population Size: 56
Sources:
Eye disorders NEC 23 patients
Disc. AE
0.05 % 4 times / day multiple, ophthalmic
Recommended
Dose: 0.05 %, 4 times / day
Route: ophthalmic
Route: multiple
Dose: 0.05 %, 4 times / day
Sources: Page: 11
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: allergic conjunctivitis
Age Group: adult
Sex: unknown
Population Size: 148
Sources: Page: 11
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
unlikely (co-administration study)
Comment: the likelihood of systemic drug interactions with drugs affecting the cytochrome P-450 is minimal
Page: 1.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
unlikely (co-administration study)
Comment: the likelihood of systemic drug interactions with drugs affecting the cytochrome P-450 is minimal
Page: 1.0
PubMed

PubMed

TitleDatePubMed
Evidence for a displaceable non-specific [3H]neurotensin binding site in rat brain.
1986 Aug
Selective effect of levocabastine on histamine receptor and histamine release from human leukocytes and guinea pig isolated tissue.
1996 Apr
Molecular cloning of a levocabastine-sensitive neurotensin binding site.
1996 May 20
Structure, functional expression, and cerebral localization of the levocabastine-sensitive neurotensin/neuromedin N receptor from mouse brain.
1996 Sep 15
Stable expression of the mouse levocabastine-sensitive neurotensin receptor in HEK 293 cell line: binding properties, photoaffinity labeling, and internalization mechanism.
1998 Feb 13
Search of antimicrobial activity of selected non-antibiotic drugs.
2002 Nov-Dec
Histamine-induced cytokine production and ICAM-1 expression in human conjunctival fibroblasts.
2002 Sep
Topical azelastine in perennial allergic conjunctivitis.
2003
[In vitro effects of antiallergic eyedrops on complement activation induced by particulate matter].
2003 Apr
Characterization of beta-lactotensin, a bioactive peptide derived from bovine beta-lactoglobulin, as a neurotensin agonist.
2003 Apr
Beta-lactotensin and neurotensin rapidly reduce serum cholesterol via NT2 receptor.
2003 Dec
Effects of fexofenadine and other antihistamines on components of the allergic response: adhesion molecules.
2003 Oct
Efficacy and safety of ketotifen eye drops in the treatment of seasonal allergic conjunctivitis.
2003 Oct
Regulation of DARPP-32 Thr75 phosphorylation by neurotensin in neostriatal neurons: involvement of glutamate signalling.
2003 Sep
The reliability, validity, and preliminary responsiveness of the Eye Allergy Patient Impact Questionnaire (EAPIQ).
2005 Oct 31
Efficacy, cost-effectiveness, and tolerability of mometasone furoate, levocabastine, and disodium cromoglycate nasal sprays in the treatment of seasonal allergic rhinitis.
2005 Sep
Potent spinal analgesia elicited through stimulation of NTS2 neurotensin receptors.
2005 Sep 7
Effect of antihistamine eye drops on the conjunctival provocation test with Japanese cedar pollen allergen.
2006 Dec
Effect of beta-lactotensin on acute stress and fear memory.
2006 Dec
Interactions between NTS2 neurotensin and opioid receptors on two nociceptive responses assessed on the hot plate test in mice.
2006 Dec 15
[Misleading advertisement on Opatanol].
2006 Jul 1
Efficacy of levocabastine hydrochloride ophthalmic suspension in the conjunctival allergen challenge test in Japanese subjects with seasonal allergic conjunctivitis.
2006 Jun
Effects of excitotoxic lesions of the medial prefrontal cortex on density of high affinity [125I-Tyr3]neurotensin binding sites within the ventral midbrain and striatum.
2006 Jun 13
Preferential inhibition of human phosphodiesterase 4 by ibudilast.
2006 May 1
The early efficacy of topical levocabastine in patients with allergic conjunctivitis.
2006 Sep
Review of azelastine nasal spray in the treatment of allergic and non-allergic rhinitis.
2007 Apr
Seasonal allergic rhinitis in adolescents and adults.
2007 Apr 1
Clinical and biological efficacy of preservative-free NAAGA eye-drops versus levocabastine eye-drops in vernal keratoconjunctivitis patients.
2007 Dec
Inhibition of release of inflammatory mediators in primary and cultured cells by a Chinese herbal medicine formula for allergic rhinitis.
2007 Feb 15
Inhibition of release of vasoactive and inflammatory mediators in airway and vascular tissues and macrophages by a chinese herbal medicine formula for allergic rhinitis.
2007 Jun
The effect of levocabastine and furosemide pretreatment on hyperreactive response after nasal provocation with hypotonic aerosol in subjects with allergic rhinitis.
2007 Nov
The effect of a combined therapy with a histamine H1 antagonist and a chemical mediator release inhibitor on allergic conjunctivitis.
2008
Neurotensin protects pancreatic beta cells from apoptosis.
2008
[Intra-annual and seasonal allergic conjunctivitis treatment: comparison of two therapeutic protocols].
2008 Dec
Drug use in children: cohort study in three European countries.
2008 Nov 24
Effectiveness of twice daily azelastine nasal spray in patients with seasonal allergic rhinitis.
2008 Oct
Randomized double-blind placebo-controlled trial of sublingual immunotherapy in children with house dust mite allergy in primary care: study design and recruitment.
2008 Oct 20
Treatment of allergic conjunctivitis with olopatadine hydrochloride eye drops.
2008 Sep
Contribution of alpha4beta1 integrin to the antiallergic effect of levocabastine.
2008 Sep 15
The effect of levocabastine hydrochloride on human Tenon's capsule fibroblasts: inhibition of proliferation, suppression of DNA synthesis and induction of apoptosis.
2009
Role of histamine H(4) receptor in allergic conjunctivitis in mice.
2009 Apr 17
beta-Lactotensin derived from bovine beta-lactoglobulin suppresses food intake via the CRF system followed by the CGRP system in mice.
2009 Dec
Evidence for a role of NTS2 receptors in the modulation of tonic pain sensitivity.
2009 Jul 6
Azelastine nasal spray for the treatment of allergic and nonallergic rhinitis.
2009 Nov
[Effect of intra nasally applied fluticasone propionate and levocabastine on the expression of aquaporin 5 in nasal mucosa of rat with experimental allergic rhinitis].
2009 Oct
NT69L, a novel analgesic, shows synergy with morphine.
2009 Oct 19
Levocabastine nasal spray significantly improves perennial allergic rhinitis: a single-blind placebo-controlled study.
2010 Aug
Relation between cooling sheet effect and tear histamine concenration in allergic conjunctivitis.
2010 Jul
Azelastine hydrochloride, a dual-acting anti-inflammatory ophthalmic solution, for treatment of allergic conjunctivitis.
2010 Sep 7
Treatment of allergic conjunctivitis: results of a 1-month, single-masked randomized study.
2010 Sep-Oct
Patents

Sample Use Guides

The usual dose is one drop instilled in affected eyes four times per day.
Route of Administration: Other
Levocabastine binds the alpha(4)beta(1) integrin and prevents eosinophil adhesion to vascular cell adhesion molecule-1 (VCAM-1), FN or human umbilical vascular endothelial cells (HUVEC) in vitro
Name Type Language
LEVOCABASTINE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
levocabastine [INN]
Common Name English
LEVOCABASTINE [VANDF]
Common Name English
Levocabastine [WHO-DD]
Common Name English
LEVOCABASTINE [MI]
Common Name English
4-PIPERIDINECARBOXYLIC ACID, 1-(4-CYANO-4-(4-FLUOROPHENYL)CYCLOHEXYL)-3-METHYL-4-PHENYL-, (-)-(1(CIS),3.ALPHA.,4.BETA.)-
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29578
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
WHO-VATC QR01AC02
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
WHO-VATC QS01GX02
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
WHO-ATC R01AC02
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
WHO-ATC S01GX02
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
Code System Code Type Description
WIKIPEDIA
LEVOCABASTINE
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY
EVMPD
SUB08465MIG
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY
NCI_THESAURUS
C61806
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY
DAILYMED
H68BP06S81
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY
CAS
79516-68-0
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY
DRUG CENTRAL
1564
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY
IUPHAR
1586
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY
LACTMED
Levocabastine
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY
MESH
C047340
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY
EPA CompTox
DTXSID1048548
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY
FDA UNII
H68BP06S81
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY
ChEMBL
CHEMBL1615438
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY
DRUG BANK
DB01106
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY
SMS_ID
100000082806
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY
RXCUI
28627
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY RxNorm
MERCK INDEX
m6785
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY Merck Index
INN
5393
Created by admin on Fri Dec 15 15:46:29 UTC 2023 , Edited by admin on Fri Dec 15 15:46:29 UTC 2023
PRIMARY