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

体外活性：依美斯汀是一种新型、强效、高亲和力、选择性的第二代 H1 受体拮抗剂，具有临床前充分记录的抗过敏作用。 Emedastine 对 H1 受体的 Ki 值为 1.3 ±0.1 nM，对 H2-（K1 为 49,067 ± 11,113 nM）和 H3-受体（Ki 为 12,430 ± 1,282 nM）的亲和力明显较弱。依美斯汀显示出与西替利嗪相当的药效学特性，因此有资格作为具有 H1 受体拮抗剂特性的安全替代化合物。可能需要更多更大规模的研究来证实单剂量给药后西替利嗪相对于依美斯汀的潜在益处。激酶测定：依美斯汀对 H1 受体（解离常数，Ki = 1.3 +/- 0.1 nM）表现出最高的亲和力，而对 H2-（K1 = 49,067 +/- 11,113 nM）和 H3 受体（Ki = 12,430 +/- 1,282 nM)。这些数据得出的 H2:H1、H3:H1 和 H2:H3 受体亲和力比分别为 37744、9562 和 4，从而使依美斯汀成为选择性很强的 H1 受体拮抗剂。依美斯汀的 H1 选择性明显优于吡拉明（H2:H1、H3:H1 和 H2:H3 比率分别为 11887、12709 和 1）。类似地，酮替芬 (858, 1752, 0.5)、左卡巴斯汀 (420, 82, 5)、苯那敏 (430, 312, 1)、扑尔敏 (5700, 2216, 3) 和安他唑林 (1163, 1110, 1) 显示这些抗组胺药的 H1 选择性也明显低于依美斯汀。依美斯汀 (IC50 = 1.44 +/- 0.3 nM) 在人小梁网细胞中拮抗组胺诱导的磷酸肌醇转换的效力与其在 H1 受体上的结合亲和力相比较。这些数据表明依美斯汀是一种高亲和力和高效的组胺拮抗剂，对 H1-组胺受体具有最高的选择性。细胞测定：

在人类中，每天服用 4 mg 依美斯汀后，浓度-时间曲线下面积 (AUC)0-24 的平均面积值为 34.49 +/- 24.07 ng h ml(-1) 和 47.05 +/- 36.12 ng h ml( -1) 分别在第 1 天和第 5 天达到。服用依美斯汀（2 mg bid）后，第1天和第5天的平均AUC0-24值分别为29.75 +/- 19.92 ng h ml(-1)和46.13 +/- 38.50 ng h ml(-1)。与安慰剂相比，依美斯汀和西替利嗪明显更有效地抑制组胺引起的风团和红肿。在药代动力学稳态水平下，西替利嗪和依美斯汀（2 mg bid）之间的药效没有显着差异。

依美斯汀对 H2- (K1 = 49,067 +/- 11,113 nM) 和 H3- (Ki = 12,430 +/- 1,282 nM) 受体的亲和力明显较弱，但对 H1-受体的亲和力最高（解离常数，Ki = 1.3 +/ - 0.1 纳米）。结果表明，依美斯汀是一种高度选择性的 H1 受体拮抗剂，H2:H1、H3:H1 和 H2:H3 受体亲和力比值分别为 37744、9562 和 4。依美斯汀的 H1 选择性显着高于吡拉明（H2:H1、H3:H1 和 H2:H3 比率分别为 11887、12709 和 1）。抗组胺药酮替芬 (858, 1752, 0.5)、左卡巴斯汀 (420, 82, 5)、苯那敏 (430, 312, 1)、扑尔敏 (5700, 2216, 3) 和安他唑啉 (1163, 1110, 1) 也显示出与依美斯汀相比，H1 选择性明显缺乏。发现美达斯汀对抗人小梁网细胞中组胺诱导的磷酸肌醇更新的能力是有效的（IC50 = 1.44 +/- 0.3 nM），这与其结合 H1 受体位点的亲和力非常一致。这些发现表明，H1-组胺受体最具选择性的组胺拮抗剂是依美斯汀，一种具有高亲和力和效力的组胺拮抗剂。

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

33.53

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)

配方 1 中的溶解度: ≥ 2.08 mg/mL (6.88 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.08 mg/mL (6.88 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (6.88 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。