在非洲爪蟾卵母细胞中，塞立洛尔（0-3 mM，90 分钟）被人肠道转运蛋白 OATP-A/1A2 吸收 [5]。 P-糖蛋白是帮助塞立洛尔（10 μM，0-50 分钟）穿过人肠上皮 (Caco-2) 细胞的几种转运蛋白之一 [6]。

在大冢朗-埃文斯德岛脂肪 (OLETF) 大鼠中，塞利洛尔（口服，100 mg/kg/天，持续 31 天）可增强动脉内皮功能，并在 OLETF 大鼠动脉内皮剥脱后 4 周恢复动脉内皮功能[2]。使用 10 mg/kg/天的饮用水治疗五周后，塞利洛尔通过刺激 PI3K-Akt 途径增加 eNOS，并抑制氧化应激、NF-κB 和信号转导。它还可以改善用醋酸脱氧皮质酮 (DOCA) 盐治疗的高血压大鼠的心血管重塑[3]。

Animal/Disease Models: Type II male Otsuka Lang-Evans Tokushima fat (OLETF) diabetic rat [2]
Doses: 100 mg/kg/day for 31 days
Route of Administration: Oral
Experimental Results: Improved acetylcholine-induced NO dependence Sexual arterial dilation. Improves tone-related basal NO release and acetylcholine-induced NO-dependent relaxation in arterial and plasma NOx.

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Animal/Disease Models: Deoxycorticosterone acetate (DOCA)-salt hypertensive rats [3]
Doses: 10 mg/kg/d for 5 weeks
Route of Administration: Drinking water treatment
Experimental Results: Activation of eNOS phosphorylation through the PI3K-Akt signaling pathway . Regulates VCAM-1 expression and is related to inhibiting NF-κB phosphorylation. Reduce ROS production by inhibiting the expression of NAD(P)H oxidase subunits p22phox, p47phox, gp91phox and nox1.

Absorption, Distribution and Excretion
Absorption of an oral dose is rapid and consistent but incomplete (55% for 200 mg dose and 74% for 400 mg dose) from the gastrointestinal tract. The bioavailability of celiprolol has been shown to be markedly affected by food and one should avoid administration of celiprolol with food. Coadministration of chlorthalidone, hydrochlorothiazide and theophylline also reduces the bioavailability of celiprolol. Following oral dosing, maximal blood concentrations are reached between 2 and 3 hours.
The distribution volume is 4.5L/kg. Celiprolol is hydrophilic and does not cross the blood-brain barrier. The binding to plasma proteins is about 25-30%.
Cleared by both renal and non-renal excretory pathways. Celiprolol is not recommended for patients with creatinine clearance less than 15 mL per minute.

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Metabolism / Metabolites
A 14C labelled dose was completely recovered within 48 hours. The first-pass effect in the liver is insignificant. Celiprolol is metabolized to a minor extent (1-3%).

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Biological Half-Life
5 hours

Protein Binding
25-30%.

[1]. Celiprolol: A Unique Selective Adrenoceptor Modulator. Cardiol Rev. Sep/Oct 2017; 25(5): 247-253.

[2]. beta1 antagonist and beta2 agonist, celiprolol, restores the impaired endothelial dependent and independent responses and decreased TNFalpha in rat with type II diabetes. Life Sci. 2007 Jan 16;80(6):592-9.

[3]. Celiprolol activates eNOS through the PI3K-Akt pathway and inhibits VCAM-1 Via NF-kappaB induced by oxidative stress. Hypertension. 2003 Nov;42(5):1004-13.

[4]. Effects of celiprolol (REV 5320), a new cardioselective beta-adrenoceptor antagonist, on in vitro adenylate cyclase, alpha- and beta-adrenergic receptor binding and lipolysis. Arch Int Pharmacodyn Ther. 1984 Nov;272(1):40-55.

[5]. Involvement of influx and efflux transport systems in gastrointestinal absorption of celiprolol. J Pharm Sci. 2009 Jul;98(7):2529-39.

[6]. Transport of celiprolol across human intestinal epithelial (Caco-2) cells: mediation of secretion by multiple transporters including P-glycoprotein. Br J Pharmacol. 1993 Nov; 110(3): 1009–1016.

3-[3-acetyl-4-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]-1,1-diethylurea is an aromatic ketone.
Celiprolol is indicated for the management of mild to moderate hypertension and effort-induced angina pectoris. It is simultaneously a selective β1 receptor antagonist, a β2 receptor partial agonist and a weak α2 receptor antagonist. In 2010 a clinical trial has suggested a use for this medication in the prevention of vascular complications of a rare inherited disease called vascular Ehlers–Danlos syndrome. This study demonstrated decreased incidence of arterial rupture or dissection (a specific type of arterial rupture in which the layers of the vessel separate prior to complete failure of the artery wall). Celiprolol is not approved for use by the FDA in the treatment of vascular Ehlers–Danlos syndrome.
A cardioselective beta-1 adrenergic antagonist that has intrinsic sympathomimetic activity. It is used in the management of ANGINA PECTORIS and HYPERTENSION.

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Drug Indication
Celiprolol is indicated for the management of mild to moderate hypertension and effort-induced angina pectoris.

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Mechanism of Action
Celiprolol is a vasoactive beta-1 selective adrenoceptor antagonist with partial beta-2 agonist activity. The beta-2 agonist activity is thought to account for its mild vasodilating properties. It lowers blood pressure in hypertensive patients at rest and on exercise. The effects on heart rate and cardiac output are dependent on the pre-existing background level of sympathetic tone. Under conditions of stress such as exercise, celiprolol attenuates chronotropic and inotropic responses to sympathetic stimulation. However, at rest minimal impairment of cardiac function is seen.

C20H33N3O4

379.49372

379.247

56980-93-9

Celiprolol-d9 hydrochloride;1215535-20-8;Celiprolol hydrochloride;57470-78-7

2663

Typically exists as solid at room temperature

1.1±0.1 g/cm3

586.5±50.0 °C at 760 mmHg

120-122

308.5±30.1 °C

0.0±1.7 mmHg at 25°C

1.545

1.92

90.9

3

5

10

27

474

0

CCN(C(NC1C=CC(OCC(CNC(C)(C)C)O)=C(C(=O)C)C=1)=O)CC

JOATXPAWOHTVSZ-UHFFFAOYSA-N

InChI=1S/C20H33N3O4/c1-7-23(8-2)19(26)22-15-9-10-18(17(11-15)14(3)24)27-13-16(25)12-21-20(4,5)6/h9-11,16,21,25H,7-8,12-13H2,1-6H3,(H,22,26)

3-(3-acetyl-4-(3-(tert-butylamino)-2-hydroxypropoxy)phenyl)-1,1-diethylurea

Edsivo RHC-5320A RHC 5320A RHC5320A

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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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。