Histamine H1 receptor (high affinity antagonist); also has affinity for H2, α1-, α2-, and 5-HT2 receptors. It demonstrates high affinity for the H1 receptor with Ki = 1.41–1.62 nM in guinea pig cerebellar and lung membranes.

Epinastine can displace specific [³H]NC-5Z binding at low concentrations in locust nervous tissue. Epinastine binds to the neuronal octopamine receptor in honey bees with Ki of 1.1 nM. Epinastine antagonises octopamine-induced cAMP formation in the insect brain[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 Ca²⁺ from the intracellular Ca store of rat peritoneal mast cells exposed to compound 48/80 and substance P, as well as the uptake of Ca²⁺ into lung mast cells[3]. One of the chemokines released by eosinophils isolated from atopic diseases, IL-8, is suppressed by epinastine in a dose- and time-dependent manner[4].
In vitro, Epinastine is a potent, selective H1 receptor antagonist with high affinity (Ki = 1.41–1.62 nM). It inhibits histamine-induced reactions in the skin or lung of rats, dogs, and guinea pigs. As a mast cell stabilizer, it inhibits the release of histamine and other inflammatory mediators from mast cells. It also has some affinity for H2, α1-, α2-, and 5-HT2 receptors.

Epinastine demonstrates a high affinity for H1-receptors in receptor binding studies in the guinea pig ileum. Epinastine prevents rats, dogs, and guinea pigs from experiencing histamine-induced reactions in their skin or lungs[1].
In vivo, Epinastine is used for the prevention of ocular itching associated with allergic conjunctivitis when administered topically as eye drops. It is an orally active antihistaminic agent that was marketed in Japan for the treatment of bronchial asthma. It inhibits histamine-induced reactions in the skin or lung of rats, dogs, and guinea pigs.

No specific cell-free H1 receptor binding assay protocol is detailed for Epinastine. For H1 receptor antagonists, typical cell-free assays include radioligand binding studies using [3H]mepyramine or [3H]pyrilamine and membrane preparations from tissues expressing H1 receptors (e.g., guinea pig cerebellum). Ki values are calculated from competition binding curves.

Cellular H1 receptor antagonism is assessed in cells expressing H1 receptors (e.g., histamine-induced calcium flux assays or histamine-induced contraction in isolated tissue preparations). Cells or tissues are treated with Epinastine and stimulated with histamine; inhibition of the response is measured. Mast cell stabilization can be assessed by measuring histamine release from mast cells upon stimulation.

In vivo efficacy is evaluated in animal models of allergic conjunctivitis or allergic rhinitis. Epinastine is administered topically (eye drops) or orally. Endpoints include ocular itching scores, conjunctival hyperemia, histamine-induced skin reactions, and inflammatory cell infiltration.

Absorption, Distribution and Excretion
The absolute bioavailability of epinastine is approximately 40%. Epinastine is primarily excreted unchanged. Renal excretion is mainly through active secretion by the renal tubules. 56 L/hr [For patients with allergic conjunctivitis, administer one drop of ELESTAT® eye drops twice daily for 7 days.] Metabolism/Metabolites Primarily excreted unchanged, less than 10% is metabolized. Biological Half-Life 12 hours
Molecular weight: 249.31 g/mol. CAS No.: 80012-43-7. Appearance: typically a powder. Solubility: soluble in DMSO and water. Storage: 2-8°C, protected from light.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Evidence from 7 subjects suggests that epinastine likely enters breast milk and results in extremely low serum concentrations in infants, making adverse effects on breastfed infants unlikely. In the United States, epinastine is only available as eye drops. Due to limited ocular absorption, no adverse effects of epinastine are expected on breastfed infants. To significantly reduce the amount of medication entering breast milk after using eye drops, press your finger against the tear duct near the corner of your eye for 1 minute or longer, then blot away excess medication with absorbent tissue.
◉ Effects on Breastfed Infants
A study of 7 lactating mothers who took 20 mg of epinastine once daily. No adverse reactions were reported in infants.
◉ Effects on Lactation and Breast Milk
Higher doses of antihistamines can lower basal serum prolactin levels in non-lactating women and early postpartum women. However, pre-treatment with antihistamines by postpartum mothers does not affect suckling-induced prolactin secretion. Prolactin levels in established lactating mothers are unlikely to affect their breastfeeding ability. Low-dose ophthalmic epinastine is unlikely to have the same effect on serum prolactin.

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Protein binding rate
64%

Epinastine has been clinically used and has a well-established safety profile. Common side effects with topical ocular use include mild eye irritation and headache. It is generally well-tolerated. No significant systemic toxicity has been reported with topical administration.

[1]. In vitro and in vivo studies of the non-sedating antihistamine epinastine. Arzneimittelforschung, 1988. 38(10): p. 1446-53.

[2]. Epinastine, a highly specific antagonist of insect neuronal octopamine receptors. Eur J Pharmacol, 1998. 349(2-3): p. 171-7.

[3]. Antiallergic effect of epinastine (WAL 801 CL) on immediate hypersensitivity reactions: (I). Elucidation of the mechanism for histamine release inhibition. Immunopharmacol Immunotoxicol, 1992. 14(1-2): p. 191-205.

[4]. A novel antiallergic drug epinastine inhibits IL-8 release from human eosinophils. Biochem Biophys Res Commun, 1997. 230(1): p. 125-8.

Epinastine is a benzodiazepine drug with the chemical name 6,11-dihydro-5H-dibenzo[b,e]azazepine, in which the azazepine ring is fused to the e-side of 4,5-dihydro-1H-imidazol-2-amine. It has anti-allergic, histamine antagonist, ophthalmic, and H1 receptor antagonist effects. It belongs to the guanidine and benzodiazepine classes. Epinastine is used to prevent itching caused by allergic conjunctivitis. It has multiple effects, inhibiting allergic reactions in three ways: 1. By stabilizing mast cells and preventing mast cell degranulation, it controls allergic reactions; 2. By preventing histamine from binding to H1 and H2 receptors, it relieves itching and provides long-lasting protection; 3. By preventing the release of pro-inflammatory chemical mediators from blood vessels, it prevents the progression of allergic reactions. Epinastine is an adrenergic receptor agonist and histamine-1 receptor inhibitor. The mechanism of action of epinastine is as an adrenergic agonist and histamine H1 receptor antagonist. Epinastine's physiological action is achieved by reducing histamine release. See also: Epinastine hydrochloride (in salt form). Drug Indications For the prevention of itching caused by allergic conjunctivitis. FDA Label Mechanism of Action Epinastine has multiple mechanisms of action, inhibiting allergic reactions in three ways: 1. By stabilizing mast cells and preventing mast cell degranulation, thus controlling allergic reactions; 2. By preventing histamine from binding to H1 and H2 receptors, thus relieving itching and providing long-lasting protection; 3. By preventing the release of pro-inflammatory chemical mediators from the bloodstream, thus preventing the progression of allergic reactions. Pharmacodynamics Epinastine is an antihistamine that inhibits the release of histamine from mast cells and is used for topical ocular administration. Epinastine is indicated for the prevention of itching caused by allergic conjunctivitis. Epinastine is a locally effective direct H1 receptor antagonist that inhibits the release of histamine from mast cells. Epinastine is selective for histamine H1 receptors and has affinity for histamine H2 receptors. In addition, epinastine also has affinity for α1, α2, and 5-HT2 receptors. Epinastine does not cross the blood-brain barrier, therefore, central nervous system side effects are not expected.
Epinastine is an FDA-approved prescription drug for the treatment of allergic conjunctivitis. It is marketed as ophthalmic solution (eye drops). It was also marketed in Japan as an orally active antihistamine for bronchial asthma. Its mechanism involves H1 receptor antagonism and mast cell stabilization.

C₁₆H₁₅N₃

249.31

249.127

C, 77.08; H, 6.06; N, 16.85

80012-43-7

Epinastine hydrochloride; 108929-04-0; Epinastine-13C,d3 hydrobromide; 127786-29-2 (HBr)

3241

White to off-white solid powder

1.32 g/cm3

428ºC at 760 mmHg

270ºC

212.7ºC

1.727

2.667

1

1

0

19

378

0

N1CC2N(C3C(CC4C2=CC=CC=4)=CC=CC=3)C=1N

WHWZLSFABNNENI-UHFFFAOYSA-N

InChI=1S/C16H15N3/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)

2,4-diazatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),3,7,9,11,14,16-heptaen-3-amine

WAL801; WAL 801; WAL-801; Epinastine; brand names Alesion, Elestat, Purivist, Relestat

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ≥ 50 mg/mL (~200.6 mM)
H2O: < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.03 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (10.03 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (10.03 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.

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 (Please use freshly prepared in vivo formulations for optimal results.)