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Epinastine (also known as WAL-801CL HCl) is a potent antihistamine H1 without sedative activity and a mast cell stabilizer that is used in eye drops for the treatment of allergic conjunctivitis. The release of histamine from mast cells is inhibited by epinastine hydrochloride, which also blocks the histamine H1 receptor. This avoids the common allergic reactions that result from histamine activation on the skin, mucous membranes, and capillaries.
Physicochemical Properties
| Molecular Formula | C₁₆H₁₅N₃ |
| Molecular Weight | 249.31 |
| Exact Mass | 249.127 |
| Elemental Analysis | C, 77.08; H, 6.06; N, 16.85 |
| CAS # | 80012-43-7 |
| Related CAS # | Epinastine hydrochloride; 108929-04-0; Epinastine-13C,d3 hydrobromide; 127786-29-2 (HBr) |
| PubChem CID | 3241 |
| Appearance | White to off-white solid powder |
| Density | 1.32 g/cm3 |
| Boiling Point | 428ºC at 760 mmHg |
| Melting Point | 270ºC |
| Flash Point | 212.7ºC |
| Index of Refraction | 1.727 |
| LogP | 2.667 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 1 |
| Rotatable Bond Count | 0 |
| Heavy Atom Count | 19 |
| Complexity | 378 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | N1CC2N(C3C(CC4C2=CC=CC=4)=CC=CC=3)C=1N |
| InChi Key | WHWZLSFABNNENI-UHFFFAOYSA-N |
| InChi Code | 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) |
| Chemical Name | 2,4-diazatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),3,7,9,11,14,16-heptaen-3-amine |
| Synonyms | WAL801; WAL 801; WAL-801; Epinastine; brand names Alesion, Elestat, Purivist, Relestat |
| 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: (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. |
| 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
| ln Vitro | 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]. |
| ln Vivo | 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]. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion The absolute bioavailability of epinastine is about 40%. Epinastine is mainly excreted unchanged. The renal elimination is mainly via active tubular secretion. 56 L/hr [patients with allergic conjunctivitis receiving one drop of ELESTAT® ophthalmic solution in each eye twice daily for seven days] Metabolism / Metabolites Mainly excreted unchanged, less than 10% metabolized. Biological Half-Life 12 hours |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Evidence from 7 individuals indicates that transfer of epinastine into breastmilk and the resulting infant serum levels are likely to be minimal and unlikely to cause adverse effects in breastfed infants. In the U.S., epinastine is only available as eye drops. Because absorption from the eye is limited, epinastine 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 In a study of 7 nursing mothers who were taking oral epinastine 20 mg once daily. No adverse reactions in the infants were reported. ◉ 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 epinastine are unlikely to have the same effect on serum prolactin. Protein Binding 64% |
| References |
[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. |
| Additional Infomation |
Epinastine is a benzazepine that is 6,11-dihydro-5H-dibenzo[b,e]azepine in which the azepine ring is fused to the e side of 4,5-dihydro-1H-imidazol-2-amine. It has a role as an anti-allergic agent, a histamine antagonist, an ophthalmology drug and a H1-receptor antagonist. It is a member of guanidines and a benzazepine. Epinastine is used for the prevention of itching associated with allergic conjunctivitis. It has a multi-action effect that inhibits the allergic response in 3 ways: 1. stabilizes mast cells by preventing mast cell degranulation to control the allergic response, 2. prevents histamine binding to both the H1- and H2-receptors to stop itching and provide lasting protection, and 3. prevents the release of proinflammatory chemical mediators from the blood vessel to halt progression of the allergic response. 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. The physiologic effect of epinastine is by means of Decreased Histamine Release. See also: Epinastine Hydrochloride (has salt form). Drug Indication For the prevention of itching associated with allergic conjunctivitis. FDA Label Mechanism of Action Epinastine has a multiaction effect that inhibits the allergic response in 3 ways: 1. stabilizes mast cells by preventing mast cell degranulation to control the allergic response, 2. prevents histamine binding to both the H1- and H2-receptors to stop itching and provide lasting protection, and 3. prevents the release of proinflammatory chemical mediators from the blood vessel to halt progression of the allergic response. Pharmacodynamics Epinastine is an antihistamine and an inhibitor of histamine release from the mast cell for topical administration to the eyes. Epinastine is indicated for the prevention of itching associated with allergic conjunctivitis. Epinastine is a topically active, direct H1-receptor antagonist and an inhibitor of the release of histamine from the mast cell. Epinastine is selective for the histamine H1-receptor and has affinity for the histamine H2 receptor. Epinastine also possesses affinity for the a1-, a2-, and 5-HT2 -receptors. Epinastine does not penetrate the blood/brain barrier and, therefore, is not expected to induce side effects of the central nervous system. |
Solubility Data
| Solubility (In Vitro) |
DMSO: ≥ 50 mg/mL (~200.6 mM) H2O: < 0.1 mg/mL |
| Solubility (In Vivo) |
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. 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. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0111 mL | 20.0554 mL | 40.1107 mL | |
| 5 mM | 0.8022 mL | 4.0111 mL | 8.0221 mL | |
| 10 mM | 0.4011 mL | 2.0055 mL | 4.0111 mL |