Bepotastine (also known as TAU 284; Bepreve) is a second generation, non-sedating, selective antagonist of histamine 1 (H1) receptor with pIC50 of 5.7. Bepostatine besilate is used to relieve pruritus, urticaria, and allergic rhinitis. By inhibiting histamine H1 receptors, bepotastine besilate counteracts the effects of histamine on the vasoconstrictor and, to a lesser extent, the vasodilator. By severing the regular flow of intracellular signals, mast cell stabilisers prevent degranulation and the subsequent release of histamine. Talion represents the brand of bepostatine besilate.
Physicochemical Properties
| Molecular Formula | C21H25CLN2O3 |
| Molecular Weight | 388.8878 |
| Exact Mass | 388.155 |
| Elemental Analysis | C, 64.86; H, 6.48; Cl, 9.12; N, 7.20; O, 12.34 |
| CAS # | 125602-71-3 |
| Related CAS # | Bepotastine besilate; 190786-44-8; Bepotastine tosylate; 1160415-45-1; 125602-71-3 |
| PubChem CID | 164522 |
| Appearance | Light brown to brown liquid |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 546.8±50.0 °C at 760 mmHg |
| Melting Point | 56-58 °C |
| Flash Point | 284.5±30.1 °C |
| Vapour Pressure | 0.0±1.5 mmHg at 25°C |
| Index of Refraction | 1.605 |
| LogP | 3.67 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 27 |
| Complexity | 449 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | C1=CC=NC(=C1)[C@H](C2=CC=C(C=C2)Cl)OC3CCN(CCCC(=O)O)CC3 |
| InChi Key | YWGDOWXRIALTES-NRFANRHFSA-N |
| InChi Code | InChI=1S/C21H25ClN2O3/c22-17-8-6-16(7-9-17)21(19-4-1-2-12-23-19)27-18-10-14-24(15-11-18)13-3-5-20(25)26/h1-2,4,6-9,12,18,21H,3,5,10-11,13-15H2,(H,25,26)/t21-/m0/s1 |
| Chemical Name | 4-[4-[(S)-(4-chlorophenyl)-pyridin-2-ylmethoxy]piperidin-1-yl]butanoic acid |
| Synonyms | TAU-284; TAU 284; TAU284; Bepotastine band name: Talion; Bepreve |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Histamine H1 receptor |
| ln Vitro |
Bepotastine (10, 100, 1000 µM; preincubates for 120 min) reduces the amount of histamine released when treated with A23187, reaching a statistically significant level at 1000 µM[1]. Bepotastine (50 µM; 1 h) inhibits the expression of NGF mRNA in NHEKs[2]. |
| ln Vivo |
Bepotastine (10 g/L; eye drop; 3 times at intervals of 20 min in one eye) significantly reduces the infiltration of conjunctival eosinophils induced by PAF[1]. Bepotastine (3 mg/kg; p.o.; once) minimizes scratching to a frequency of 59.0 and a duration of 14.57 seconds, which is nearly identical to the control[3]. Bepotastine (10 mg/kg; p.o.; once) significantly suppresses serum LTB 4 levels to 711.3 pg/mL at 1 h and 858.8 pg/mL at 2 h in NC/Nga mice with a rash[3]. |
| Cell Assay |
Cell Line: RPMCs Concentration: 10, 100, 1000 µM Incubation Time: 120 min (preincubate) Result: Decreased the release of histamine |
| Animal Protocol |
Guinea pigs (6-week-old) 10 g/L (1.0% (w/v)) for 10 µL Eye drop; 3 times at intervals of 20 min (in one eye). |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Tmax, after single dose, opthalmic = 1.2 hours; Cmax, 1.5%, opthalmic dose = 7.3 ±1.9 ng/mL; After 24 hours post-installation, levels of bepotastine are below quantifiable limit of 2 ng/mL. Minimal systemic absorption with opthalmic dosage form. When a oral dose of 2.5 - 40 mg bepotastine is given, 75%-90% of the dose was excreted unchanged in the urine by 24 hours. Metabolism / Metabolites Minimal metabolism via CYP enzymes Biological Half-Life Elimination half life = 2.5 hours |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation There are no reports of infants breastfed during maternal therapy with bepotastine. Because absorption from the eye is limited, bepotastine 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 bepotastine was not found as of the revision date. In one telephone follow-up study, mothers reported irritability and colicky symptoms in 10% of infants exposed to various antihistamines and drowsiness was reported in 1.6% of infants. None of the reactions required medical attention and none of the patients were using bepotastine. ◉ 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. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. Low ophthalmic doses of bepotastine are unlikely to have the same effect on serum prolactin. Protein Binding 55.4% mean plasma protein binding with 10 mg oral dose. Extent of protein binding is independent of plasma drug concentration. |
| References |
[1]. Bepotastine besilate, a highly selective histamine H(1) receptor antagonist, suppresses vascular hyperpermeability and eosinophil recruitment in in vitro and in vivo experimental allergic conjunctivitis models. Exp Eye Res. 2010 Jul;91(1):8. [2]. Bepotastine besilate downregulates the expression of nerve elongation factors in normal human epidermal keratinocytes. J Dermatol Sci. 2018 Apr 23:S0923-1811(18)30186-5. [3]. Oral administration of bepotastine besilate suppressed scratching behavior of atopic dermatitis model NC/Nga mice. Int Arch Allergy Immunol. 2008;145(4):277-82. [4]. Non-clinical pharmacology, pharmacokinetics, and safety findings for the antihistamine bepotastine besilate. Curr Med Res Opin. 2010 Oct;26(10):2329-38. |
| Additional Infomation |
Bepotastine is an ether that is (S)-(4-chlorophenyl)(pyridin-2-yl)methanol in which the hydroxyl hydrogen is substituted by a 1-(3-carboxypropyl)piperidin-4-yl group. A topical, selective and non-sedating histamine (H1) receptor antagonist used (as its benzenesulfonate salt) for treatment of itching associated with allergic conjunctivitis. It has a role as a H1-receptor antagonist and an anti-allergic agent. It is a member of pyridines, a monocarboxylic acid, a member of piperidines, an ether and a member of monochlorobenzenes. It is a conjugate base of a bepotastine(1+). Bepotastine is a non-sedating, selective antagonist of the histamine 1 (H1) receptor. Bepotastine was approved in Japan for use in the treatment of allergic rhinitis and uriticaria/puritus in July 2000 and January 2002, respectively, and is marketed by Tanabe Seiyaku Co., Ltd. under the brand name Talion. It is available in oral and opthalmic dosage forms in Japan. The opthalmic solution is FDA approved since Sept 8, 2009 and is under the brand name Bepreve. Bepotastine is a Histamine-1 Receptor Antagonist. Drug Indication For the symptomatic treatment of itchy eyes (caused by IgE-induced mast cell degranulation) due to allergic conjunctivitis. FDA Label Mechanism of Action Because of a type 1 hypersensitivity reaction cascade that is triggered by antigen exposure, allergic conjunctivitis occurs. Allergen exposure is followed by conjunctival mast cell degranulation and histamine released as a result of the formation of complementary IgE cross-links on the conjunctiva. Due to the release of histamine, symptoms such as itching can be observed. Bepotastine works to relieve itchy eyes by three primary mechanisms of action. It is a non-sedating, selective antagonist of the histamine 1 (H1) receptor, a mast cell stabilizer, and it suppresses the migration of eosinophils into inflamed tissues to prevent tissue damage and worsening of allergic inflammation of the conjunctiva. Pharmacodynamics Bepotastine is a non-sedating, selective antagonist of the histamine 1 (H1) receptor. It belongs to the second-generation piperidine chemical class. It is a mast cell stabilizer and suppresses the migration of eosinophils into inflamed tissues. Furthermore, bepotastine does not interact with serotonin, muscarinic, benzodiazepine, and beta-adrenergic receptor that would otherwise result in adverse reactions such as dry mouth or sonmolence. Onset of action = 0.25 hours; Duration of action = 12-24 hours; |
Solubility Data
| Solubility (In Vitro) |
DMSO: 78~100 mg/mL (200.6~257.1 mM) Water: ~78 mg/mL Ethanol: ~78 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.43 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5714 mL | 12.8571 mL | 25.7142 mL | |
| 5 mM | 0.5143 mL | 2.5714 mL | 5.1428 mL | |
| 10 mM | 0.2571 mL | 1.2857 mL | 2.5714 mL |