LEVOCABASTINE

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 Search

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

Molecular Formula	C26H29FN2O2
Molecular Weight	420.5191
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=420b3f66-87f0-47d8-947c-541e84eb594a
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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H1 receptor 312 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11915520	Antagonist 2737
Neurotensin receptor type 2 3 Target ID: O95665 Gene ID: 23620.0 Gene Symbol: NTSR2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/8647296	Inverse Agonist 78

Conditions

Condition	Modality	Targets	Highest Phase	Product
Seasonal allergic conjunctivitis 3 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=420b3f66-87f0-47d8-947c-541e84eb594a	Palliative		Approved 8307	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

C_max

Value	Dose	Analyte	Population
7.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7907347/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/8549024/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/8549024/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/8549024/	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

Value	Dose	Analyte	Population
319 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7907347/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/8549024/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/8549024/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/8549024/	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

T_1/2

Value	Dose	Analyte	Population
35.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7907347/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/8549024/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/8549024/	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

F_unbound

Value	Dose	Analyte	Population
45% REVIEW https://pubmed.ncbi.nlm.nih.gov/8549024/	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% REVIEW https://pubmed.ncbi.nlm.nih.gov/8549024/	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% REVIEW https://pubmed.ncbi.nlm.nih.gov/8549024/	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

Dose	Population	Adverse 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: https://db.cbg-meb.nl/veegactie/csp/Levocabastine_okt2014.pdf 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: https://db.cbg-meb.nl/veegactie/csp/Levocabastine_okt2014.pdf Page: 12	Disc. AE: Headache, Blepharoconjunctivitis... AEs leading to discontinuation/dose reduction: Headache (3 patients) Blepharoconjunctivitis (3 patients) Sources: https://db.cbg-meb.nl/veegactie/csp/Levocabastine_okt2014.pdf 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: https://www.researchgate.net/publication/5375238_Levocabastine_eye_drops_are_effective_and_well_tolerated_for_the_treatment_of_allergic_conjunctivitis_in_children	unhealthy, < 12 years n = 177 Health Status: unhealthy Condition: allergic conjunctivitis Age Group: < 12 years Sex: M+F Population Size: 177 Sources: https://www.researchgate.net/publication/5375238_Levocabastine_eye_drops_are_effective_and_well_tolerated_for_the_treatment_of_allergic_conjunctivitis_in_children	Other AEs: Eye disorders NEC... Other AEs: Eye disorders NEC (33 patients) Sources: https://www.researchgate.net/publication/5375238_Levocabastine_eye_drops_are_effective_and_well_tolerated_for_the_treatment_of_allergic_conjunctivitis_in_children
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: https://www.researchgate.net/publication/5375238_Levocabastine_eye_drops_are_effective_and_well_tolerated_for_the_treatment_of_allergic_conjunctivitis_in_children	unhealthy, > 12 years n = 56 Health Status: unhealthy Condition: allergic conjunctivitis Age Group: > 12 years Sex: M+F Population Size: 56 Sources: https://www.researchgate.net/publication/5375238_Levocabastine_eye_drops_are_effective_and_well_tolerated_for_the_treatment_of_allergic_conjunctivitis_in_children	Other AEs: Eye disorders NEC... Other AEs: Eye disorders NEC (7 patients) Sources: https://www.researchgate.net/publication/5375238_Levocabastine_eye_drops_are_effective_and_well_tolerated_for_the_treatment_of_allergic_conjunctivitis_in_children
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: https://db.cbg-meb.nl/veegactie/csp/Levocabastine_okt2014.pdf Page: 11	unhealthy, adult n = 148 Health Status: unhealthy Condition: allergic conjunctivitis Age Group: adult Sex: unknown Population Size: 148 Sources: https://db.cbg-meb.nl/veegactie/csp/Levocabastine_okt2014.pdf Page: 11	Disc. AE: Eye disorders NEC... AEs leading to discontinuation/dose reduction: Eye disorders NEC (23 patients) Sources: https://db.cbg-meb.nl/veegactie/csp/Levocabastine_okt2014.pdf 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: https://pubmed.ncbi.nlm.nih.gov/10088031/	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: https://pubmed.ncbi.nlm.nih.gov/10088031/	Sources: https://pubmed.ncbi.nlm.nih.gov/10088031/

AEs

AE	Significance	Dose	Population
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: https://db.cbg-meb.nl/veegactie/csp/Levocabastine_okt2014.pdf 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: https://db.cbg-meb.nl/veegactie/csp/Levocabastine_okt2014.pdf 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: https://db.cbg-meb.nl/veegactie/csp/Levocabastine_okt2014.pdf 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: https://db.cbg-meb.nl/veegactie/csp/Levocabastine_okt2014.pdf 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: https://www.researchgate.net/publication/5375238_Levocabastine_eye_drops_are_effective_and_well_tolerated_for_the_treatment_of_allergic_conjunctivitis_in_children	unhealthy, < 12 years n = 177 Health Status: unhealthy Condition: allergic conjunctivitis Age Group: < 12 years Sex: M+F Population Size: 177 Sources: https://www.researchgate.net/publication/5375238_Levocabastine_eye_drops_are_effective_and_well_tolerated_for_the_treatment_of_allergic_conjunctivitis_in_children
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: https://www.researchgate.net/publication/5375238_Levocabastine_eye_drops_are_effective_and_well_tolerated_for_the_treatment_of_allergic_conjunctivitis_in_children	unhealthy, > 12 years n = 56 Health Status: unhealthy Condition: allergic conjunctivitis Age Group: > 12 years Sex: M+F Population Size: 56 Sources: https://www.researchgate.net/publication/5375238_Levocabastine_eye_drops_are_effective_and_well_tolerated_for_the_treatment_of_allergic_conjunctivitis_in_children
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: https://db.cbg-meb.nl/veegactie/csp/Levocabastine_okt2014.pdf Page: 11	unhealthy, adult n = 148 Health Status: unhealthy Condition: allergic conjunctivitis Age Group: adult Sex: unknown Population Size: 148 Sources: https://db.cbg-meb.nl/veegactie/csp/Levocabastine_okt2014.pdf Page: 11

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 450 18	CYP 450 31

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 450 20	inhibitor 3185 Sources: https://accp1.onlinelibrary.wiley.com/doi/abs/10.1177/00912709922007589 Page: 1.0	no		unlikely (co-administration study) Comment: the likelihood of systemic drug interactions with drugs affecting the cytochrome P-450 is minimal Sources: https://accp1.onlinelibrary.wiley.com/doi/abs/10.1177/00912709922007589 Page: 1.0

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 450 31	substrate 3264 Sources: https://accp1.onlinelibrary.wiley.com/doi/abs/10.1177/00912709922007589 Page: 1.0	no		unlikely (co-administration study) Comment: the likelihood of systemic drug interactions with drugs affecting the cytochrome P-450 is minimal Sources: https://accp1.onlinelibrary.wiley.com/doi/abs/10.1177/00912709922007589 Page: 1.0

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P0058MI
ABI Chem	AC1L1GWR
AN PharmaTech	AN-6364
Achemtek	0102-012957	http://www.achemtek.com/79516-68-0
Alfa Chemistry	80185-65-5
BOC Sciences	80185-65-5
BePharm Ltd.	B136220
ChemMol	49401013	http://www.chemmol.com/chemmol/49401013.html
Chemieliva Pharmaceutical Co., Ltd	PBCM0841436
Clearsynth	CS-AD-00421	http://www.clearsynth.com/en/CSAD00421.html
Compound Cloud	54384
Compound Cloud	54385
Hairui	HR139897
Nanjing Pope Bio-tech	NSTH-D02017
Norris Pharm	NSTH-D02017
NovoSeek	54385
Oxchem Corporation	AX8136220
Smolecule	S532933	http://www.smolecule.com/products/s532933
THE BioTek	bt-273330	https://www.thebiotek.com/product/inhibitors/bt-273330
THE BioTek	bt-404790	https://www.thebiotek.com/product/others/bt-404790
W&J PharmaChem	100424
ZINC	ZINC000000586239	http://zinc15.docking.org/substances/ZINC000000586239
eNovation Chemicals	D674472	https://www.enovationchem.com/ProductDetails.asp?ProductID=D674472

PubMed

Title	Date	PubMed
Evidence for a displaceable non-specific [3H]neurotensin binding site in rat brain.	1986 Aug	3022160
Stable expression of the mouse levocabastine-sensitive neurotensin receptor in HEK 293 cell line: binding properties, photoaffinity labeling, and internalization mechanism.	1998 Feb 13	9480852
Emedastine and allergic conjunctivitis: new preparation. Poor assessment.	2001 Apr	11718155
Localization of neurotensin NTS2 receptors in rat brain, using.	2001 Apr 17	11303751
Agonism, inverse agonism, and neutral antagonism at the constitutively active human neurotensin receptor 2.	2001 Dec	11723247
SR48692 is a neurotensin receptor antagonist which inhibits the growth of small cell lung cancer cells.	2001 Jan	11179604
Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study).	2002 Feb	11842293
Receptor-mediated internalization of [3H]-neurotensin in synaptosomal preparations from rat neostriatum.	2002 Jun	12128010
[Pharmacological and clinical properties of levocabastine hydrochloride (eye drop and nasal spray), a selective H1 antagonist].	2002 Mar	11915520
Actual therapeutic management of allergic and hyperreactive nasal disorders.	2004	22073046
Comparative efficacy of olopatadine 0.1% ophthalmic solution versus levocabastine 0.05% ophthalmic suspension using the conjunctival allergen challenge model.	2004 Dec	15701212
Efficacy and tolerability of ophthalmic epinastine: a randomized, double-masked, parallel-group, active- and vehicle-controlled environmental trial in patients with seasonal allergic conjunctivitis.	2004 Jan	14996515
Effect of ketotifen fumarate, olopatadine, and levocabastine on ocular active anaphylaxis in the guinea pig and ocular immediate hypersensitivity in the albino rat.	2005 Feb	15804768
[Comparison of three antiallergic eyedrops in a specific conjunctival provocation test: mequitazine, levocabastine and dexamethasone].	2005 Mar	15883488
Increasing effect by simultaneous use of levocabastine and pemirolast on experimental allergic conjunctivitis in rats.	2005 Mar	15744071
Identification and functional characterization of a 5-transmembrane domain variant isoform of the NTS2 neurotensin receptor in rat central nervous system.	2005 Mar 18	15637074
[Misleading advertisement on Opatanol].	2006 Jul 1	16875272
The effect of levocabastine and furosemide pretreatment on hyperreactive response after nasal provocation with hypotonic aerosol in subjects with allergic rhinitis.	2007 Nov	17618447
Neurotensin protects pancreatic beta cells from apoptosis.	2008	18456542
Treatment of allergic conjunctivitis with olopatadine hydrochloride eye drops.	2008 Sep	19668750
Evidence for a role of NTS2 receptors in the modulation of tonic pain sensitivity.	2009 Jul 6	19580660
NT69L, a novel analgesic, shows synergy with morphine.	2009 Oct 19	19651107
Levocabastine nasal spray significantly improves perennial allergic rhinitis: a single-blind placebo-controlled study.	2010 Aug	20138720
Relation between cooling sheet effect and tear histamine concenration in allergic conjunctivitis.	2010 Jul	20606377

Patents

Sample Use Guides

In Vivo Use Guide

The usual dose is one drop instilled in affected eyes four times per day.

Route of Administration: Other

In Vitro Use Guide

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

Substance Class	Chemical Created by `admin` on `Fri Dec 16 18:07:48 UTC 2022` Edited by `admin` on `Fri Dec 16 18:07:48 UTC 2022`
Record UNII	H68BP06S81
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LEVOCABASTINE

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