| Size | Price | Stock | Qty |
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| 25mg |
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Purity: ≥98%
Epinastine HCl (WAL801CL; Alesion; Elestat; Epinastine; Epinastin; WAL-801CL), the hydrochloride salt of epinastine, is a potent antagonist of histamine H1 receptors without sedative side effects. It also functions as a mast cell stabilizer and is found in eye drops that are used to treat allergic conjunctivitis. The release of histamine from mast cells is inhibited by paroxetine, which also blocks the histamine H1 receptor. This stops histamine activity on capillaries, skin, and mucous membranes from causing the usual allergic symptoms.
| Targets |
Histamine receptor
Histamine H1 receptor (H1R) (human H1R, Ki=0.6 nM; rat H1R, Ki=0.8 nM) [1] Histamine H2 receptor (H2R), muscarinic receptors, adrenergic receptors (Ki>1000 nM, negligible affinity) [1] |
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| ln Vitro |
In vitro activity: Epinastine demonstrates a high affinity for H1-receptors in guinea pig ileum receptor binding experiments.[1] In locust nerve tissue, epinastine can displace certain [ 3 H]NC-5Z binding at low concentrations. With a Ki of 1.1 nM, epinastine binds to the neuronal octopamine receptor in honey bees. In the insect brain, epinastine inhibits the formation of cAMP induced by octopamine.[2] Epinastine inhibits the release of histamine from peritoneal mast cells in rats that is brought on by compound 48/80 and the antigen-antibody reaction. Comparably, epinastine inhibits the release of histamine from isolated rat peritoneal mast cells as well as from rat mesenterial pieces when compound 48/80 is present. In actively sensitized guinea pigs, epinastine effectively inhibits both the release of Ca 2+ from the intracellular Ca store of rat peritoneal mast cells exposed to compound 48/80 and substance P, as well as the uptake of Ca 2+ into lung mast cells.[3] When eosinophils from atopic diseases are isolated, they release IL-8, one of the chemokines for them. Epinastine has a dose- and time-dependent suppressive effect on this chemokine.[4]
Radioligand binding assay showed Epinastine HCl (WAL801) competitively bound to human and rat H1R with high affinity, displacing [3H]-mepyramine in a concentration-dependent manner [1] - Isolated guinea pig tracheal smooth muscle strips pre-contracted with histamine (1 μM) were treated with Epinastine HCl (WAL801) (0.1 μM-10 μM). The drug induced concentration-dependent relaxation, with an IC50 of 1.1 μM, confirming H1R antagonistic activity [2] - Human peripheral blood basophils stimulated with anti-IgE (1 μg/mL) were treated with Epinastine HCl (WAL801) (1 nM-10 μM). It dose-dependently inhibited histamine release, with maximum inhibition of 68% at 10 μM [3] - Cultured rat peritoneal mast cells were activated with compound 48/80 (1 μg/mL). Epinastine HCl (WAL801) (0.5 μM-50 μM) suppressed mast cell degranulation and histamine release by 55% at 50 μM, without affecting cell viability [3] |
| ln Vivo |
Epinastine inhibits the effects of histamine on guinea pigs, dogs, and rats' skin or lungs.[1]
Passive cutaneous anaphylaxis (PCA) model in rats: Oral administration of Epinastine HCl (WAL801) (0.3 mg/kg, 1 mg/kg, 3 mg/kg) 1 hour before antigen challenge dose-dependently inhibited skin wheal formation, with 83% inhibition at 3 mg/kg [1] - Allergic rhinitis model in guinea pigs: Intranasal ovalbumin challenge induced sneezing and rhinorrhea. Intraperitoneal injection of Epinastine HCl (WAL801) (1 mg/kg) 30 minutes before challenge reduced sneezing frequency by 65% and nasal secretion by 58% [2] - Acute urticaria model in mice: Intravenous injection of Epinastine HCl (WAL801) (0.5 mg/kg, 1 mg/kg) inhibited histamine-induced skin edema by 42% and 67% respectively, compared to vehicle group [1] |
| Enzyme Assay |
H1R binding assay: Prepare membrane fractions from human H1R-expressing HEK293 cells or rat brain tissue. Incubate membranes with [3H]-mepyramine (0.5 nM) and various concentrations of Epinastine HCl (WAL801) (0.01 nM-100 nM) at 25°C for 60 minutes. Separate bound and free ligand by vacuum filtration through glass fiber filters. Measure radioactivity with a liquid scintillation counter and calculate Ki values using the Cheng-Prusoff equation [1]
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| Cell Assay |
Basophil histamine release assay: Isolate human peripheral blood basophils via density gradient centrifugation. Resuspend cells in buffer and pre-treat with Epinastine HCl (WAL801) (1 nM-10 μM) for 30 minutes. Stimulate with anti-IgE (1 μg/mL) for 60 minutes at 37°C. Centrifuge to collect supernatant and measure histamine concentration via fluorometric assay [3]
- Mast cell degranulation assay: Isolate rat peritoneal mast cells by peritoneal lavage. Suspend cells in culture medium and pre-treat with Epinastine HCl (WAL801) (0.5 μM-50 μM) for 15 minutes. Stimulate with compound 48/80 (1 μg/mL) for 30 minutes. Centrifuge to collect supernatant, and detect histamine levels via colorimetric assay [3] - Tracheal smooth muscle relaxation assay: Isolate guinea pig tracheal strips, mount in organ baths with oxygenated Krebs-Ringer solution (37°C, 95% O2/5% CO2), and equilibrate for 60 minutes. Pre-contract with histamine (1 μM), then add Epinastine HCl (WAL801) (0.1 μM-10 μM) cumulatively and record tension changes [2] |
| Animal Protocol |
PCA rat model: Male Wistar rats (150-200 g) were intradermally injected with anti-ovalbumin IgE (0.1 mL) on the back. After 48 hours, Epinastine HCl (WAL801) was dissolved in physiological saline and administered via oral gavage (0.3 mg/kg, 1 mg/kg, 3 mg/kg). One hour later, intravenous injection of ovalbumin (1 mg/kg) + Evans blue (5 mg/kg) was given. Thirty minutes later, rats were euthanized, and skin wheal area was measured [1]
- Allergic rhinitis guinea pig model: Male Hartley guinea pigs (300-350 g) were sensitized with ovalbumin (100 μg) + aluminum hydroxide (2 mg) via intraperitoneal injection on days 0 and 7. On day 14, Epinastine HCl (WAL801) (1 mg/kg) was injected intraperitoneally 30 minutes before intranasal ovalbumin challenge (1% solution). Record sneezing frequency and nasal secretion volume for 10 minutes post-challenge [2] - Acute urticaria mouse model: Male ICR mice (20-25 g) were intravenously injected with Epinastine HCl (WAL801) (0.5 mg/kg, 1 mg/kg) or physiological saline. Thirty minutes later, histamine (10 μg) was injected intradermally into the ear. Two hours later, measure ear thickness to evaluate edema severity [1] - Pharmacokinetic rat experiment: Male Sprague-Dawley rats (200-250 g) were fasted for 12 hours. Epinastine HCl (WAL801) was administered via oral gavage (10 mg/kg) or intravenous injection (2 mg/kg). Blood samples were collected at predetermined time points, and plasma drug concentrations were determined by HPLC [1] |
| ADME/Pharmacokinetics |
Absorption: The oral bioavailability in rats is 65-75%; peak plasma concentration (Cmax) is reached 1.5-2.5 hours after oral administration [1]
- Distribution: The volume of distribution (Vd) in rats is 10-12 L/kg; the brain/plasma concentration ratio is 0.08, indicating extremely low blood-brain barrier penetration [1] - Metabolism: Very little is metabolized in the liver (≤15% of the dose), and most (85%) is excreted unchanged [1] - Excretion: 60% of the dose is excreted in the urine (55% unchanged, 5% metabolites), and 35% is excreted in the feces. The elimination half-life (t1/2) in rats is 7-9 hours [1] |
| Toxicity/Toxicokinetics |
Plasma protein binding rate: The plasma protein binding rate of Epinastine HCl (WAL801) in human plasma is 88-92%, and the plasma protein binding rate in rat plasma is 85-90%[1]. Acute toxicity: The LD50 of rats is >2000 mg/kg (oral) and 1500 mg/kg (intraperitoneal injection); the LD50 of mice is >1800 mg/kg (oral)[1]. Chronic toxicity: No obvious hepatotoxicity or hematological abnormalities were observed in rats after oral administration of Epinastine HCl (WAL801) (100 mg/kg/day) for 6 consecutive months[1]. Clinical side effects: Mild headache (3-5% of patients) and dry mouth (1-2%) have been reported. Due to the extremely low blood-brain barrier penetration, no sedative effect or cognitive impairment was observed at therapeutic doses[1,2].
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| References | |
| Additional Infomation |
Epinastine hydrochloride is a histamine H1 receptor antagonist and has no sedative effect. Epinastine hydrochloride blocks histamine H1 receptors, inhibiting histamine release from mast cells. This prevents typical allergic reactions caused by histamine acting on capillary, skin, mucous membranes, and gastrointestinal and bronchial smooth muscle. Typical effects of histamine include vasodilation, bronchoconstriction, increased vascular permeability, pain, itching, and spasmodic contractions of gastrointestinal smooth muscle. Epinastine also has affinity for histamine H2, 5-HT2, and α1 and α2 adrenergic receptors.
See also: Epinastine (containing the active fraction). Epistine hydrochloride (WAL801) is a second-generation non-sedating histamine H1 receptor antagonist with a dual mechanism of action: competitive blocking of H1R and inhibition of histamine release from mast cells/basophils [1,3]. It is indicated for the treatment of allergic rhinitis (relieving sneezing, runny nose, and nasal itching) and chronic idiopathic urticaria (relieving wheals and itching) [1,2]. Compared to first-generation antihistamines, it has high selectivity for H1R and very low blood-brain barrier penetration, thus avoiding sedative side effects [1]. It has a rapid onset of action (within 1 hour of administration) and a long duration of action (12-24 hours), supporting once- or twice-daily administration [1]. |
| Molecular Formula |
C16H16CLN3
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| Molecular Weight |
285.77
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| Exact Mass |
285.103
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| Elemental Analysis |
C, 67.25; H, 5.64; Cl, 12.41; N, 14.70
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| CAS # |
108929-04-0
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| Related CAS # |
Epinastine; 80012-43-7
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| PubChem CID |
157313
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| Appearance |
White to off-white solid powder
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| Density |
1.32g/cm3
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| Boiling Point |
428ºC at 760 mmHg
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| Melting Point |
>270ºC
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| Flash Point |
212.7ºC
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| Vapour Pressure |
1.56E-07mmHg at 25°C
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| LogP |
3.469
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
20
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| Complexity |
378
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl[H].N12C(N([H])[H])=NC([H])([H])C1([H])C1=C([H])C([H])=C([H])C([H])=C1C([H])([H])C1=C([H])C([H])=C([H])C([H])=C21
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| InChi Key |
VKXSGUIOOQPGAF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H15N3.ClH/c17-16-18-10-15-13-7-3-1-5-11(13)9-12-6-2-4-8-14(12)19(15)16;/h1-8,15H,9-10H2,(H2,17,18);1H
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| Chemical Name |
2,4-diazatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),3,7,9,11,14,16-heptaen-3-amine;hydrochloride
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| Synonyms |
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.28 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 20.8 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: ≥ 2.08 mg/mL (7.28 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (7.28 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 20 mg/mL (69.99 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4993 mL | 17.4966 mL | 34.9932 mL | |
| 5 mM | 0.6999 mL | 3.4993 mL | 6.9986 mL | |
| 10 mM | 0.3499 mL | 1.7497 mL | 3.4993 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02182518 | Completed | Drug: Epinastine Drug: Placebo |
Rhinitis, Allergic, Perennial | Boehringer Ingelheim | May 2000 | Phase 3 |
| NCT02260063 | Completed | Drug: Epinastine syrup Drug: Epinastine tablets |
Healthy | Boehringer Ingelheim | November 1998 | Phase 1 |
| NCT02182531 | Completed | Drug: Epinastine Drug: Pseudoephedrine |
Healthy | Boehringer Ingelheim | August 1999 | Phase 1 |
| NCT02260037 | Completed | Drug: Epinastine nasal Drug: Placebo |
Healthy | Boehringer Ingelheim | August 2001 | Phase 1 |
| NCT01382654 | Completed | Drug: epinastine 0.1% Drug: epinastine 0.2% |
Allergic Rhinitis | Merck Sharp & Dohme LLC | September 2006 | Phase 2 |
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