H₁ Receptor ( Ki = 1.3 nM ); H₂ Receptor ( Ki = 49067 nM ); H₃ Receptor ( Ki = 12430 nM )

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].

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.

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

Absorption, Distribution and Excretion
Ophthalmic use of emedastine usually does not produce measurable plasma concentrations.
Following oral administration, approximately 44% of the total dose can be recovered in the urine over the 24-hour period, with only 3.6% of the dose excreted as unchanged form. Two primary metabolites, 5- and 6-hydroxyemedastine, are excreted in the urine as both free and conjugated forms.

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Metabolism / Metabolites
Two primary metabolites, 5-hydroxyemedastine and 6-hydroxyemedastine, are excreted in the urine as both free and conjugated forms. Minor metabolites include the 5'-oxoanalogs of 5-hydroxyemedastine and 6-hydroxy-emedastine and the N-oxide.

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Biological Half-Life
The elimination half-life in the plasma is 3-4 hours following oral administration.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Emedastine is an antihistamine that is not approved for marketing in the United States by the U.S. Food and Drug Administration, but is available in other countries. Preliminary data indicate that oral administration of 2 mg daily produces low levels in milk and does not affect the breastfed infant.
When used as an eye drop, emedastine 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
A woman was prescribed emedastine difumarate 2 mg once daily and pranlukast hydrate 112.5 mg twice daily during pregnancy and postpartum. Her infant was breastfed and no adverse effects were noted.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

[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 1-Methyl-1,4-diazepane in which the hydrogen attached to the nitrogen at position 4 is substituted by a 1-(2-ethoxyethyl)-1H-benzimidazol-2-yl group. A relatively selective histamine H1 antagonist, it is used as the difumatate salt for allergic rhinitis, urticaria, and pruritic skin disorders, and in eyedrops for the symptomatic relief of allergic conjuntivitis. It has a role as a H1-receptor antagonist, an anti-allergic agent and an antipruritic drug.
Emedastine is an antihistamine used in 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 anti-allergic activity. Emedastine reversibly and competitively blocks histamine by binding to H1 receptors, thus blocking its downstream activity. As a result this agent interferes with mediator release from mast cells either by inhibiting calcium ion influx across mast cell/basophil plasma membrane or by inhibiting intracellular calcium ion release within the cells. In addition, emedastine may also inhibit the late-phase allergic reaction mediated through leukotrienes or prostaglandins, or by producing an anti-platelet activating factor effect. Upon ocular administration, emedastine causes a dose-dependent inhibition of histamine-stimulated vascular permeability in the conjunctiva. Emedastine does not affect adrenergic, dopamine, or serotonin receptors.

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

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Mechanism of Action
Emedastine is a relatively selective, histamine H₁ antagonist. In vitro examinations of emedastine's affinity for histamine receptors demonstrate relative selectivity for the H₁ histamine receptor. In vivo studies have shown concentration-dependent inhibition of histamine-stimulated vascular permeability in the conjunctiva following topical ocular administration. Emedastine appears exert negligible effects on adrenergic, dopaminergic and serotonin receptors.

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Pharmacodynamics
Emedastine is a relatively selective H₁-receptor antagonist.

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.)