| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Levocabastine (R-50547) is a long acting and selective antihistaminic (histamine H1-receptor antagonist) with anti-allergic activity. It is used for allergic conjunctivitis. Also a neurotensin receptor subtype 2 (NTR2) antagonist (Ki = 17 nM for mNTR2).
| ln Vitro |
Levocabastine (0-1000 μM; HEK-293 cells) exhibits a concentration-dependent effect on the binding of 125I-FN to the α4β1 integrin linked with SPA beads, with an IC50 of 406.2 μm [3]. Levocarbastine (0-1000 μM; 30 min; EoL-1 and Jurkat cells) suppresses in vitro the α4β1 integrin/VCAM-1-mediated cell adhesion. Levocabastine inhibits the α4β1 integrin-dependent adhesion of Jurkat cells to VCAM-1, exhibiting an IC50 of 395.6 μM, and an IC50 of 403.6 μM for EoL-1 cells. Furthermore, human eosinophil adherence to VCAM-1-coated wells can be inhibited by levocabastine (IC50=443.7 μM) [3].
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| ln Vivo |
Levocarbastine (R 50547; 0.25 mg/kg; intraperitoneally; twice daily for five days; administered to parainfluenza 3 (PI-3) virus-infected guinea pigs) prevents hyperresponsiveness of the airways caused by the virus [1]. Levocarbastine (0.05 mg/kg; single intraperitoneal injection; male C57BL/6J mice) can prevent β-LT's behavioral anti-stress effect [2]. Levocarbastine causes allergic conjunctivitis (AC) and a marked elevation of conjunctival VLA-4 when administered once to ovalbumin-sensitized guinea pigs (500 µg/eye; eye drops) [3].
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| Animal Protocol |
Animal/Disease Models: Parainfluenza-3 (PI-3) virus guinea pig [1]
Doses: 0.25 mg/kg Route of Administration: intraperitoneal (ip) injection; twice (two times) daily for five days Experimental Results: Inhibition of bronchoalveolar cell influx and increased albumin content . Animal/Disease Models: Male C57BL/6J mice (8-9 weeks old) [2] Doses: 0.05 mg/kg; 30 mg/kg (β-LT) Route of Administration: intraperitoneal (ip) injection; primary Experimental Results:blocking β-LT Anti-anxiety effect and reduce the number of head bowing. Animal/Disease Models: Ovalbumin-sensitized guinea pigs [3] Doses: 500 µg/eye Route of Administration: One eye drop Experimental Results: Significant protective effect on allergic conjunctivitis (AC) and preventing the increase in conjunctival VLA-4 and conjunctival eosinophilic infiltration. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
After instillation in the eye, levocabastine is systemically absorbed, albeit at low levels. Metabolism / Metabolites Mostly unchanged. 10 to 20% is metabolized to the acylglucuronide of levocabastine. Biological Half-Life 36 hours (after oral administration) |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation Because absorption from the eye is limited, levocabastine would not be expected to cause any adverse effects in breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue. ◉ Effects in Breastfed Infants Relevant published information on levocabastine was not found as of the revision date. In one telephone follow-up study, mothers reported irritability and colicky symptoms 10% of infants exposed to various antihistamines and drowsiness was reported in 1.6% of infants. None of the reactions required medical attention. ◉ Effects on Lactation and Breastmilk Antihistamines in relatively high doses given by injection can decrease basal serum prolactin in nonlactating women and in early postpartum women. However, suckling-induced prolactin secretion is not affected by antihistamine pretreatment of postpartum mothers. Whether lower oral doses of antihistamines have the same effect on serum prolactin or whether the effects on prolactin have any consequences on breastfeeding success have not been studied. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. |
| References | |
| Additional Infomation |
Levocabastine is a member of piperidines.
Levocabastine is a selective second-generation H1-receptor antagonist used for allergic conjunctivitis. Levocabastine was discovered at Janssen Pharmaceutica in 1979. Levocabastine is a synthetic piperidine derivative with antihistamine properties. Levocabastine is a second generation histamine-1 receptor antagonist. When applied locally into the eye as a topical solution, this agent reduces itching, rhinorrhea and symptoms of allergic rhinitis or conjunctivitis. Drug 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. 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. 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. |
| Molecular Formula |
C26H29N2O2F
|
|---|---|
| Molecular Weight |
420.51906
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| Exact Mass |
420.221
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| CAS # |
79516-68-0
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| Related CAS # |
Levocabastine hydrochloride;79547-78-7
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| PubChem CID |
54385
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.23 g/cm3
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| Boiling Point |
589.9ºC at 760 mmHg
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| Flash Point |
310.5ºC
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| Index of Refraction |
1.606
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| LogP |
4.831
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
|
| Heavy Atom Count |
31
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| Complexity |
681
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@@H]1CN(CC[C@@]1(C2=CC=CC=C2)C(=O)O)C3CCC(CC3)(C#N)C4=CC=C(C=C4)F
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| InChi Key |
ZCGOMHNNNFPNMX-YHYDXASRSA-N
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| InChi Code |
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
|
| Chemical Name |
(3S,4R)-1-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-3-methyl-4-phenylpiperidine-4-carboxylic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3780 mL | 11.8900 mL | 23.7801 mL | |
| 5 mM | 0.4756 mL | 2.3780 mL | 4.7560 mL | |
| 10 mM | 0.2378 mL | 1.1890 mL | 2.3780 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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