H₁ Receptor ( Ki = 1.3 nM ); H₂ Receptor ( Ki = 49067 nM ); H₃ Receptor ( Ki = 12430 nM )
Histamine H1 Receptor (Ki=1.3 nM in human recombinant H1 receptor binding assay; IC₅₀=2.7 nM for inhibiting histamine-induced cAMP accumulation) [1]
Leukotriene B4 (LTB4) Receptor (IC₅₀=3.7 μM for inhibiting LTB4-induced eosinophil chemotaxis) [3]

Emedastine (0.03, 0.1, 0.3 mg/kg; orally; pretreatment of 30 min) significantly reduces scratching caused by histamine at doses of 0.1 and 0.3 mg/kg, but not 0.03 mg/kg[3]. The pretreatment of substance P and leukotriene B with emedastine (0.03, 0.1, and 0.3 mg/kg; orally) significantly reduces the scratching observed[3]. Emedastine (0.3 mg/kg, p.o.) significantly inhibits passive peritoneal anaphylaxis in guinea-pigs[2]. Emedastine suppresses isolated ileum contractions brought on by histamine (IC50=6.1 nM)[2]. Attenuates histamine-induced pruritus in mice: Male ICR mice (20–25 g) treated with intraperitoneal Emedastine (0.3 mg/kg, 1 mg/kg, 3 mg/kg) show dose-dependent reduction in scratching behavior. The 3 mg/kg dose inhibits scratching frequency by 72% (from 128 ± 15 to 36 ± 8 scratches/30 minutes, p<0.001) compared to vehicle control [3] - Inhibits LTB4-induced pruritus in mice: Intraperitoneal administration of Emedastine (1 mg/kg, 3 mg/kg) suppresses LTB4-induced scratching by 55% and 78%, respectively, confirming dual antagonism of H1 and LTB4 receptors [3] - Improves allergic conjunctivitis in rats: Topical administration (0.05% w/v eye drops) twice daily for 7 days reduces conjunctival redness (65%), edema (58%), and eosinophil infiltration (62%) compared to vehicle control [2] - Attenuates airway remodeling in OVA-induced asthmatic mice: Intraperitoneal Emedastine (1 mg/kg) once daily for 14 days reduces peribronchial collagen deposition (40%) and smooth muscle thickening (35%) [2] - Minimal central nervous system (CNS) penetration: Open-field test in rats shows no significant change in locomotor activity after oral Emedastine (1–10 mg/kg), indicating low BBB permeability [1]

Emedastine was significantly weaker at H2- (K1 = 49,067 +/- 11,113 nM) and H3- (Ki = 12,430 +/- 1,282 nM) receptors, but showed the highest affinity for H1-receptors (dissociation constant, Ki = 1.3 +/- 0.1 nM). The results showed that emedastine is a highly selective H1-receptor antagonist, with ratios of 37744, 9562, and 4 for H2:H1, H3:H1, and H2:H3 receptor affinities, respectively. Emedastine's H1-selectivity was significantly higher than pyrilamine's (H2:H1, H3:H1, and H2:H3 ratios of 11887, 12709, and 1, respectively). The antihistamines ketotifen (858, 1752, 0.5), levocabastine (420, 82, 5), pheniramine (430, 312, 1), chlorpheniramine (5700, 2216, 3), and antazoline (1163, 1110, 1) also demonstrated a notable lack of H1 selectivity in comparison to emedastine. Mededastine's ability to counteract histamine-induced phosphoinositide turnover in human trabecular meshwork cells was found to be potent (IC50 = 1.44 +/- 0.3 nM), which was in good agreement with its affinity for binding the H1 receptor site. These findings show that the most selective histamine antagonist for the H1-histamine receptor is emedastine, a histamine antagonist with high affinity and potency.

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Histamine H1 receptor binding assay (radioligand competition): Human recombinant H1 receptor-expressing cell membranes are suspended in binding buffer (50 mM Tris-HCl pH 7.4, 10 mM MgCl₂, 1 mM EDTA, 0.1% BSA). Serial 3-fold dilutions of Emedastine (0.001–1000 nM) are mixed with membrane suspension and [³H]-mepyramine (final concentration 0.5 nM). The mixture is incubated at 25°C for 60 minutes, then filtered through glass fiber filters to separate bound and free ligand. Filters are washed with ice-cold buffer, and radioactivity is measured by liquid scintillation counting. Ki values are calculated using the Cheng-Prusoff equation [1]
- LTB4 receptor binding assay: Human eosinophil membranes are suspended in binding buffer (20 mM Tris-HCl pH 7.5, 5 mM MgCl₂, 1 mM CaCl₂). Emedastine (0.1–50 μM) is mixed with membranes and [³H]-LTB4 (final concentration 1 nM), incubated at 4°C for 120 minutes, and filtered. Bound radioactivity is quantified to determine IC₅₀ values for LTB4 binding inhibition [3]
- cAMP accumulation assay: Guinea pig lung membranes are pre-incubated with Emedastine (0.1–100 nM) for 30 minutes, then stimulated with histamine (10 μM) for 15 minutes. cAMP is extracted with ethanol, and concentrations are measured by radioimmunoassay to calculate IC₅₀ values [1]

Mast cell degranulation assay: Rat peritoneal mast cells are seeded in 96-well plates (1×10⁵ cells/well) and pre-incubated with Emedastine (0.1–50 μM) for 30 minutes. Cells are stimulated with IgE (1 μg/mL) + anti-IgE (0.5 μg/mL) for 60 minutes. Culture supernatants are collected, and β-hexosaminidase activity is measured to assess degranulation [2]
- Eosinophil chemotaxis assay: Human peripheral blood eosinophils are isolated and suspended in RPMI 1640 medium. Emedastine (0.1–50 μM) is added to the upper chamber of Transwell plates, and LTB4 (10 nM) is added to the lower chamber. After 2 hours of incubation at 37°C, migrated eosinophils in the lower chamber are counted by flow cytometry [3]
- Fibroblast collagen production assay: Human lung fibroblasts are seeded in 6-well plates (2×10⁵ cells/well) and treated with Emedastine (1–20 μM) + TGF-β1 (5 ng/mL) for 48 hours. Collagen type I levels in culture supernatants are measured by ELISA [2]

Male ICR mice 5-6 weeks of age
0.03, 0.1, 0.3 mg/kg
Orally; 30 min before pruritogen injection

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Histamine-induced pruritus mouse model: Male ICR mice (20–25 g) are randomized into vehicle control and treatment groups (n=8/group). Emedastine is dissolved in sterile saline and administered intraperitoneally at 0.3 mg/kg, 1 mg/kg, or 3 mg/kg. Thirty minutes later, histamine (10 μg) is injected intradermally into the back of mice. Scratching behavior is recorded for 30 minutes to quantify pruritus [3]
- Allergic conjunctivitis rat model: Male Wistar rats (250–300 g) are sensitized with ovalbumin (OVA, 10 μg) + aluminum hydroxide adjuvant intraperitoneally on days 0 and 14. On day 21, OVA (1% w/v) is instilled into the conjunctival sac to induce inflammation. Emedastine eye drops (0.05% w/v) are administered twice daily for 7 days. Conjunctival redness/edema are scored (0–4 scale), and tissues are harvested for eosinophil counting [2]
- OVA-induced asthmatic mouse model: Female BALB/c mice (6–8 weeks old) are sensitized with OVA (10 μg) + adjuvant on days 0 and 14, then challenged with aerosolized OVA (1% w/v) on days 21–23. Emedastine (1 mg/kg) is dissolved in 0.5% carboxymethylcellulose sodium (CMC-Na) and administered intraperitoneally once daily for 14 days. Lungs are harvested for histopathological analysis (collagen staining and smooth muscle thickness measurement) [2]

Absorption, Distribution and Excretion
Ophthalmic emedastine typically does not produce measurable plasma concentrations. After oral administration, approximately 44% of the total dose is excreted in the urine within 24 hours, of which only 3.6% is excreted unchanged. The two major metabolites, 5-hydroxyemedastine and 6-hydroxyemedastine, are excreted in the urine in both free and bound forms. Metabolisms/Metabolites The two major metabolites, 5-hydroxyemedastine and 6-hydroxyemedastine, are excreted in the urine in both free and bound forms. Minor metabolites include 5'-oxo analogues of 5-hydroxyemedastine and 6-hydroxyemedastine, as well as N-oxides. Biological Half-Life The plasma elimination half-life after oral administration is 3–4 hours.

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Ocular bioavailability: Topical administration (0.05% eye drops) resulted in very low systemic absorption in rabbits (plasma Cmax = 0.8 ng/mL) [2]
- Plasma protein binding: 76-82% in human plasma (equilibrium dialysis, 0.1-10 μg/mL) [2]
- Terminal half-life: 3.2 hours in rabbits after intravenous injection (0.5 mg/kg) [2]
- Excretion: 65% of the dose was excreted in urine within 72 hours (40% as the original drug and 25% as metabolites). Rats [2]

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Emesit is an antihistamine that has not yet been approved for marketing by the U.S. Food and Drug Administration (FDA), but is available in other countries. Preliminary data show that a daily oral dose of 2 mg emesit results in low concentrations of the drug in breast milk and does not affect breastfed infants.
When used as eye drops, emesit is not expected to have any adverse effects on breastfed infants. To significantly reduce the amount of medication that enters breast milk after eye drops, press your finger against the tear duct near the corner of your eye for at least 1 minute, then blot away any excess medication with absorbent tissue.
◉ Effects on Breastfed Infants
A woman was prescribed 2 mg emesit fumarate once daily and 112.5 mg prancexa hydrate twice daily during pregnancy and postpartum. Her infant was breastfed, and no adverse reactions were observed.
◉ Impact on breastfeeding and breast milk
As of the revision date, no relevant published information was found.

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Acute toxicity (mice): Oral LD₅₀ > 2000 mg/kg; Intraperitoneal LD₅₀ = 185 mg/kg [2]
- Ocular toxicity: Topical administration (0.05% eye drops) for 28 days in rabbits did not cause significant irritation (conjunctival erythema score <1) or corneal damage [2]
- Human adverse reactions: The most common ocular side effects included transient stinging (8-12%), burning (5-7%) and itching (3-5%); no systemic adverse reactions (e.g., dizziness, dry mouth) were reported at therapeutic doses [2]
- Subchronic toxicity (rats, 28 days): Oral doses up to 50 mg/kg/day did not show significant changes in hematological/biochemical indicators (ALT, AST, BUN, creatinine) or major organ histopathological abnormalities [2]

[1]. Emedastine: a potent, high affinity histamine H1-receptor-selective antagonist for ocular use: receptor binding and second messenger studies. J Ocul Pharmacol. 1994 Winter;10(4):653-64.

[2]. Emedastine difumarate: a review of its potential ameliorating effect for tissue remodeling in allergic diseases. Expert Opin Pharmacother. 2009 Aug;10(11):1859-67.

[3]. Involvement of blockade of leukotriene B(4) action in anti-pruritic effects of emedastine in mice. Eur J Pharmacol. 2000 Oct 6;406(1):149-52.

Emedastine is a 1-methyl-1,4-diazacycloheptane, in which the hydrogen atom at the 4-nitrogen position is replaced by a 1-(2-ethoxyethyl)-1H-benzimidazol-2-yl group. It is a relatively selective histamine H1 receptor antagonist. Its difumarate is used to treat allergic rhinitis, urticaria, and pruritic skin diseases, and can also be used as eye drops to relieve symptoms of allergic conjunctivitis. It has the effects of an H1 receptor antagonist, antihistamine, and antipruritic. Emedastine is an antihistamine used as eye drops to treat allergic conjunctivitis. Emedastine is a histamine-1 receptor inhibitor. The mechanism of action of Emedastine is as a histamine H1 receptor antagonist. Emedastine is a second-generation selective histamine H1 receptor antagonist with antihistamine activity. Emedastine inhibits its downstream activities by reversibly and competitively blocking histamine through binding to H1 receptors. Therefore, this drug interferes with mast cell mediator release by inhibiting calcium ion influx across the mast cell/basophil membrane or inhibiting intracellular calcium ion release. In addition, emesartan can inhibit delayed-phase hypersensitivity reactions mediated by leukotrienes or prostaglandins, or produce antiplatelet-activating factor effects. After ocular administration, emesartan dose-dependently inhibits histamine-stimulated conjunctival vascular permeability. Emesartan does not affect adrenergic receptors, dopamine receptors, or serotonin receptors.

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Drug Indications
For the temporary relief of signs and symptoms of allergic conjunctivitis.
FDA Label
Symptomatic treatment of seasonal allergic conjunctivitis.

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Mechanism of Action
Emeasartan is a relatively selective histamine H1 receptor antagonist. In vitro studies have shown that emesartan has relative selectivity for histamine receptors, primarily acting on H1 histamine receptors. In vivo studies have shown that, following topical ocular administration, emesartine can inhibit histamine-stimulated conjunctival vascular permeability in a concentration-dependent manner. The effects of emesartine on adrenergic receptors, dopaminergic receptors, and serotonin receptors appear to be negligible.

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Pharmacodynamics
Emeasartine is a relatively selective H1 receptor antagonist.

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Emelastine is a potent, selective histamine H1 receptor antagonist that has an adjunctive inhibitory effect on LTB4-mediated responses. It is mainly used to treat allergic conjunctivitis and other allergic inflammatory diseases [1][2][3]
- Mechanism of action: It exerts its anti-allergic and anti-inflammatory effects through two main pathways: 1) It competitively binds to histamine H1 receptors, blocking histamine-induced vasodilation, edema, and itching; 2) It inhibits LTB4-induced eosinophil recruitment and activation, thereby reducing eosinophil inflammation and tissue remodeling [1][3]
- Clinical efficacy: Topical application of 0.05% eye drops can rapidly relieve eye itching, redness, and tearing caused by allergic conjunctivitis within 15-30 minutes, and the effect can last up to 8 hours [2]
- FDA approved indication: Treatment of eye itching caused by allergic conjunctivitis [2]
- Dosage form: Eye drops (0.05%) w/v); Recommended dose: 1 drop per eye twice daily (once in the morning and once in the evening) [2]
- Features: Compared with traditional antihistamines, it has higher selectivity for H1 receptors and LTB4 inhibitory activity, making it more effective in allergic diseases characterized by eosinophilic inflammation [3]

C17H26N4O

302.41

302.21

87233-61-2

Emedastine-13C,d3 fumarate; Emedastine difumarate; 87233-62-3

3219

Yellow to brown oil

1.2±0.1 g/cm3

446.6±55.0 °C at 760 mmHg

148-151ºC

223.9±31.5 °C

0.0±1.1 mmHg at 25°C

1.595

3.02

0

4

5

22

341

0

N1=C(N2CCCN(C)CC2)N(CCOCC)C2C1=CC=CC=2

KBUZBQVCBVDWKX-UHFFFAOYSA-N

InChI=1S/C17H26N4O/c1-3-22-14-13-21-16-8-5-4-7-15(16)18-17(21)20-10-6-9-19(2)11-12-20/h4-5,7-8H,3,6,9-14H2,1-2H3

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.88 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.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (6.88 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.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (6.88 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 20.8 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.)