Histamine H1 receptor ( IC50 = 51 nM )

体外活性：地氯雷他定是卡巴胆碱诱导的离体兔虹膜平滑肌收缩的竞争性拮抗剂，pA2 为 6.67。地氯雷他定与人 H1 受体结合，取代氚化美吡拉敏，Ki 值为 0.87 nM。 Desloratadine（100 nM 至 10 μM）抑制人嗜碱性粒细胞 IgE 介导和非 IgE 介导的细胞因子 IL-4 和 IL-13 的产生。 Desloratadine（300 nM 至 100 μM）抑制人外周血嗜碱性粒细胞中 IgE 和非 IgE 介导的组胺释放。地氯雷他定（0.1 μM 至 10 μM）还可以抑制血小板活化因子诱导的嗜酸性粒细胞趋化性和 TNF-α 诱导的嗜酸性粒细胞粘附（从过敏性鼻炎或过敏性哮喘患者获得的嗜酸性粒细胞）。 Desloratadine (1 μM-10 μM) 剂量依赖性地抑制人嗜碱性粒细胞释放组胺和 LTC4。 Desloratadine (0.1 μM-10 μM) 剂量依赖性地抑制被人类嗜碱性粒细胞的 IL-3 和 PMA 激活的嗜碱性粒细胞的 IL-13 分泌。地氯雷他定 (10 μM) 预处理可导致培养的嗜碱性粒细胞中诱导的细胞因子信息显着减少。地氯雷他定 (10 μM) 预处理可使培养的嗜碱性粒细胞中因抗 IgE 激活而积累的 IL-4 信息减少约 80%。 Desloratadine (10 μM) 还抑制分泌到培养的嗜碱性粒细胞上清液中的组胺和 IL-4 蛋白。激酶测定：Desloratadine(Sch34117) 是一种有效的人组胺 H1 受体拮抗剂，用于治疗过敏。目标：组胺 H1 受体 地氯雷他定与人 H1 受体结合，取代氚化美吡拉敏，Ki 值为 0.87 nM。 Desloratadine (100 nM 至 10 μM) 可抑制人嗜碱性粒细胞 IgE 介导和非 IgE 介导的细胞因子 IL-4 和 IL-13 的产生。细胞测定：地氯雷他定（300 nM 至 100 μM）抑制人外周血嗜碱性粒细胞中 IgE 和非 IgE 介导的组胺释放。地氯雷他定（0.1 μM 至 10 μM）还可以抑制血小板活化因子诱导的嗜酸性粒细胞趋化性和 TNF-α 诱导的嗜酸性粒细胞粘附（从过敏性鼻炎或过敏性哮喘患者获得的嗜酸性粒细胞）。 Desloratadine (1 μM-10 μM) 剂量依赖性地抑制人嗜碱性粒细胞释放组胺和 LTC4。 Desloratadine (0.1 μM-10 μM) 剂量依赖性地抑制被人类嗜碱性粒细胞的 IL-3 和 PMA 激活的嗜碱性粒细胞的 IL-13 分泌。地氯雷他定 (10 μM) 预处理可导致培养的嗜碱性粒细胞中诱导的细胞因子信息显着减少。地氯雷他定 (10 μM) 预处理可使培养的嗜碱性粒细胞中因抗 IgE 激活而积累的 IL-4 信息减少约 80%。 Desloratadine (10 μM) 还抑制分泌到培养的嗜碱性粒细胞上清液中的组胺和 IL-4 蛋白。 [3H]地氯雷他定与 CHO 细胞中表达的人组胺 H1 受体结合，Kd 为 1.1 nM。在竞争结合研究中，地氯雷他定的效力分别比西替利嗪、依巴斯汀、非索非那定和氯雷他定强 52 倍、57 倍、194 倍和 153 倍。

Desloratadine (1 mg/mL、3 mg/mL 和 10 mg/mL) 在豚鼠体内诱导剂量依赖性且持久的瞳孔散大。 Desloratadine 可抑制组胺引起的小鼠爪水肿，ED50 为 0.15 mg/kg。地氯雷他定可抑制豚鼠上呼吸道组胺激发时微血管通透性的增加，ED50 为 0.9 μg。 Desloratadine (5 mg/kg) 通过破坏清醒小鼠的血脑屏障来抑制氧化震颤素引起的震颤。 Desloratadine (1.0 mg/kg) 显着抑制氧化震颤素诱导的 (0.00125 mg/kg、0.0025 mg/kg 和 0.02 mg/kg) dP/dt 降低，表现为剂量反应曲线向右移动鼠。 Desloratadine (1.0 mg/kg) 显着抑制氧化震颤素诱导的 (0.00125 mg/kg、0.0025 mg/kg 和 0.02 mg/kg) dP/dt 降低，表现为剂量反应曲线向右移动鼠

Absorption, Distribution and Excretion
Desloratadine administered orally for ten days to healthy volunteers as a 5 mg tablet once daily resulted in a mean Tmax of approximately 3 hours, a mean steady-state Cmax of 4 ng/ml, and a mean steady-state AUC of 56.9 ng\*hr/ml. A similar profile was observed using 10 ml of an oral solution containing 5 mg of desloratadine. Food was found not to affect desloratadine absorption.
Approximately 87% of a ¹⁴C-desloratadine dose was equally recovered in urine and feces as metabolic products.

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Metabolism / Metabolites
Desloratadine is metabolized to the active metabolite 3-hydroxydesloratadine, which is subsequently glucuronidated.
Desloratadine is a known human metabolite of Rupatadine and loratadine.

Route of Elimination: Desloratadine (a major metabolite of loratadine) is extensively metabolized to 3-hydroxydesloratadine, an active metabolite, which is subsequently glucuronidated. Approximately 87% of a 14C-desloratadine dose was equally recovered in urine and feces.
Half Life: 50 hours

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Biological Half-Life
Desloratadine has a mean plasma elimination half-life of approximately 27 hours.

Toxicity Summary
Like other H1-blockers, Desloratadine competes with free histamine for binding at H₁-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms (eg. nasal congestion, watery eyes) brought on by histamine.

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because of its expected low milk levels and lack of sedation and anticholinergic effects, maternal use of desloratadine is unlikely to affect a breastfed infant or milk production. Desloratadine might have a negative effect on lactation in combination with a sympathomimetic agent such as pseudoephedrine.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ 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. Whether lower oral doses of antihistamines have the same effect on serum prolactin or whether the effects on prolactin have any consequences on breastfeeding success have not been studied. The prolactin level in a mother with established lactation may not affect her ability to breastfeed

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Protein Binding
Desloratadine is bound approximately 82 to 87% to plasma proteins, while its active metabolite, 3-hydroxydesloratadine, is bound approximately 85 to 89%.

[1]. Eur J Pharmacol . 1999 Jun 18;374(2):249-54.

[2]. J Allergy Clin Immunol . 2001 Apr;107(4):751-62.

[3]. Clin Exp Allergy . 2001 Sep;31(9):1369-77.

[4]. Eur J Pharmacol . 2002 Aug 9;449(3):229-37.

[5]. BMC Pharmacol . 2005 Aug 18:5:13.

Desloratadine is loratadine in which the ethoxycarbonyl group attached to the piperidine ring is replaced by hydrogen. The major metabolite of loratidine, desloratadine is an antihistamine which is used for the symptomatic relief of allergic conditions including rhinitis and chronic urticaria. It does not readily enter the central nervous system, so does not cause drowsiness. It has a role as a H1-receptor antagonist, an anti-allergic agent, a cholinergic antagonist and a drug metabolite.
Desloratadine is a second generation, tricyclic antihistamine that which has a selective and peripheral H1-antagonist action. It is the active descarboethoxy metabolite of loratidine (a second generation histamine). Desloratidine has a long-lasting effect and does not cause drowsiness because it does not readily enter the central nervous system.
Desloratadine is a Histamine-1 Receptor Antagonist. The mechanism of action of desloratadine is as a Histamine H1 Receptor Antagonist.
Desloratadine has been reported in Bos taurus with data available.
Desloratadine is a long-acting piperidine derivate with selective H1 antihistaminergic and non-sedating properties. Desloratadine diminishes the typical histaminergic effects on H1-receptors in bronchial smooth muscle, capillaries and gastrointestinal smooth muscle, including vasodilation, bronchoconstriction, increased vascular permeability, pain, itching and spasmodic contractions of gastrointestinal smooth muscle. Desloratadine is used to provide symptomatic relieve of allergic symptoms.
Desloratadine is a second generation, tricyclic antihistamine that which has a selective and peripheral H1-antagonist action. It is the active descarboethoxy metabolite of loratidine (a second generation histamine). Desloratidine has a long-lasting effect and does not cause drowsiness because it does not readily enter the central nervous system.
See also: Desloratadine; pseudoephedrine sulfate (component of).

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Drug Indication
For the relief of symptoms of seasonal allergic rhinitis, perennial (non-seasonal) allergic rhinitis. Desloratidine is also used for the sympomatic treatment of pruritus and urticaria (hives) associated with chronic idiopathic urticaria.
FDA Label
Neoclarityn is indicated for the relief of symptoms associated with: allergic rhinitisurticaria
Aerius is indicated for the relief of symptoms associated with: allergic rhinitis; urticaria.
Azomyr is indicated for the relief of symptoms associated with: allergic rhinitis (see section 5. 1)urticaria (see section 5. 1)
Treatment of allergic rhinitis and urticaria.
Desloratadine ratiopharm is indicated in adults for the relief of symptoms associated with: allergic rhinitischronic idiopathic urticaria as initially diagnosed by a physician
Desloratadine Teva is indicated for the relief of symptoms associated with: allergic rhinitis; urticaria.
Dasselta is indicated for the relief of symptoms associated with: allergic rhinitis; urticaria.
Aerius is indicated for the relief of symptoms associated with: - allergic rhinitis (see section 5. 1)- urticaria (see section 5. 1)
Opulis is indicated for the relief of symptoms associated with: - allergic rhinitis (see section 5. 1)- urticaria (see section 5. 1)

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Mechanism of Action
Like other H1-blockers, Desloratadine competes with free histamine for binding at H₁-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms (eg. nasal congestion, watery eyes) brought on by histamine.

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Pharmacodynamics
Desloratadine is a long-acting second-generation H₁-receptor antagonist which has a selective and peripheral H1-antagonist action. Histamine is a chemical that causes many of the signs that are part of allergic reactions, such as the swelling of tissues. Histamine is released from histamine-storing cells (mast cells) and attaches to other cells that have receptors for histamine. The attachment of the histamine to the receptors causes the cell to be "activated," releasing other chemicals which produce the effects that we associate with allergies. Desloratadine blocks one type of receptor for histamine (the H1 receptor) and thus prevents activation of cells by histamine. Unlike most other antihistamines, Desloratadine does not enter the brain from the blood and, therefore, does not cause drowsiness.

C19H19CLN2

310.82

310.123

C, 73.42; H, 6.16; Cl, 11.41; N, 9.01

100643-71-8

Desloratadine-d4; 381727-29-3; Desloratadine-d9; 1795024-82-6; Desloratadine-3,3,5,5-d4; 2713301-38-1; Desloratadine-d5; 1020719-34-9

124087

White to off-white solid powder

1.2±0.1 g/cm3

467.9±45.0 °C at 760 mmHg

150-151°C

236.8±28.7 °C

0.0±1.2 mmHg at 25°C

1.626

6.77

24.92

1

2

0

22

425

0

ClC1C([H])=C([H])C2=C(C=1[H])C([H])([H])C([H])([H])C1C([H])=C([H])C([H])=NC=1/C/2=C1\C([H])([H])C([H])([H])N([H])C([H])([H])C\1([H])[H]

JAUOIFJMECXRGI-UHFFFAOYSA-N

InChI=1S/C19H19ClN2/c20-16-5-6-17-15(12-16)4-3-14-2-1-9-22-19(14)18(17)13-7-10-21-11-8-13/h1-2,5-6,9,12,21H,3-4,7-8,10-11H2

13-chloro-2-piperidin-4-ylidene-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene

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: ≥ 2.5 mg/mL (8.04 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 25.0 mg/mL澄清DMSO储备液加入到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: ≥ 2.5 mg/mL (8.04 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 25.0 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: ≥ 2.5 mg/mL (8.04 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 25.0 mg/mL 澄清 DMSO 储备液添加到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 30% Propylene glycol , 5% Tween 80 , 65% D5W: 30 mg/mL

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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。