β1 adrenoceptor β2 adrenoceptor β3 adrenoceptor

Bopindolol是β1-和β2-肾上腺素受体（AR）的非选择性拮抗剂，通过药理学、分子生物学技术和分子建模发现，它具有几种独特的性质。Bopindolol可持续阻断β1-和β2-AR，具有内在的拟交感神经和膜稳定作用，抑制肾素分泌，并与5-HT受体相互作用。此外，我们最近的分子建模研究确定了bopindolol和β-AR亚型之间可能的相互作用位点。经审查的研究支持了我们的发现，即博平多洛尔对β1-和β2-AR没有选择性，对β3-AR亚型的亲和力低，并且具有可能有益于治疗心血管疾病的药理学特性[4]。

波吲洛尔（静脉注射；8、16 和 32 μg/kg）对麻醉犬的疗效是普萘洛尔的四倍，并且以剂量依赖性方式抑制异丙肾上腺素诱发的心动过速[1]。二吲哚洛尔（0.3、1 和 3 mg/kg；IP；单剂量）对心率和舒张压的影响具有剂量依赖性[2]。 动物模型：雄性 Wistar 大鼠（260-300 g）[2] 剂量：0.3、1 和 3 mg/kg 给药方式：IP；单剂量结果：舒张压产生剂量依赖性降低，3 mg/kg 时降低约 8 mmHg。以剂量依赖性方式降低心率。

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1.比较了具有部分激动剂活性的β肾上腺素受体拮抗剂博平多洛尔和博平多洛对髓心大鼠舒张压和心率的影响。2.bopindolol和pindolol均能降低髓心大鼠的舒张压（DBP）。Bopindolol（3.0mg/kg）和pindolol（1.0mg/kg）在DBP方面产生了约8mmHg的类似下降；因此，与博平多洛尔相比，平多洛尔的降压效力高出3倍。3.这两种药物都会使心率呈剂量依赖性下降。4.普萘洛尔（5mg/kg）对博平多洛尔或平多洛尔产生的DBP降低没有拮抗作用。5.这些结果表明，博匹多洛尔和匹多洛尔都通过一些独立于β肾上腺素受体的机制降低了髓内大鼠的DBP和心率[2]。

Animal/Disease Models: Male Wistar rats (260-300 g)[2]
Doses: 0.3, 1 and 3 mg/kg
Route of Administration: IP; single dosage
Experimental Results: Produced dose dependent decreases in diastolic blood pressure, and the decrease of about 8 mmHg at 3 mg/kg. diminished the heart rate in a dose-dependent manner.

Bopindolol is a nonselective beta-adrenoceptor antagonist [corrected] with partial agonist activity which is used in the treatment of hypertension. The drug is rapidly metabolised to an active hydrolysed form. The antihypertensive effects of bopindolol 0.5 to 4 mg are sustained for more than 24 hours after once daily dosing, and the drug appears similar in efficacy to propranolol, metoprolol, atenolol, pindolol and slow release nifedipine in the treatment of mild to moderate forms of this disease. In limited trials bopindolol has also successfully reduced symptoms in patients with angina pectoris, anxiety and essential tremor. Thus, bopindolol is an effective and well-tolerated beta-adrenoceptor antagonist. [1]

636368 rat LD50 oral 824 mg/kg SENSE ORGANS AND SPECIAL SENSES: PTOSIS: EYE; BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD; GASTROINTESTINAL: ULCERATION OR BLEEDING FROM STOMACH Kiso to Rinsho. Clinical Report., 23(4369), 1989
636368 rat LD50 subcutaneous 481 mg/kg BEHAVIORAL: ATAXIA; LUNGS, THORAX, OR RESPIRATION: CYANOSIS; SKIN AND APPENDAGES (SKIN): HAIR: OTHER Kiso to Rinsho. Clinical Report., 23(4369), 1989
636368 mouse LD50 oral 228 mg/kg Drugs in Japan, -(1293), 1995
636368 rabbit LD50 oral 318 mg/kg Drugs in Japan, -(1293), 1995
636368 rat LD50 intravenous 9200 ug/kg SENSE ORGANS AND SPECIAL SENSES: MYDRIASIS (PUPILLARY DILATION): EYE; BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD; LUNGS, THORAX, OR RESPIRATION: OTHER CHANGES Kiso to Rinsho. Clinical Report., 23(4369), 1989

[1]. Bopindolol. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy. Drugs.

[2]. Hypotensive effect of bopindolol in pithed rats. Gen Pharmacol. 1993 Mar;24(2):373-5.

[3]. Bopindolol is a slowly dissociating beta 1-adrenoceptor antagonist when compared to other beta-blockers. Biol Pharm Bull. 1995 Aug;18(8):1066-71.

[4]. Bopindolol: pharmacological basis and clinical implications. Cardiovasc Drug Rev. 2001 Spring;19(1):9-24.

1-(tert-butylamino)-3-[(2-methyl-1H-indol-4-yl)oxy]propan-2-yl benzoate is a methylindole that is 2-methyl-1H-indol-4-ol in which the hydrogen of the hydroxy group is replaced by a 2-(benzoyloxy)-3-(tert-butylamino)propyl group. It is a methylindole, a secondary amino compound, an aromatic ether and a benzoate ester.
Bopindolol (INN) is an ester prodrug for the beta blocker [pindolol].

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Drug Indication
For the management of hypertension, edema, ventricular tachycardias, and atrial fibrillation.

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Mechanism of Action
Bopindolol (as pindolol) non-selectively blocks beta-1 adrenergic receptors mainly in the heart, inhibiting the effects of epinephrine and norepinephrine resulting in a decrease in heart rate and blood pressure. By binding beta-2 receptors in the juxtaglomerular apparatus, Pindolol inhibits the production of renin, thereby inhibiting angiotensin II and aldosterone production and therefore inhibits the vasoconstriction and water retention due to angiotensin II and aldosterone, respectively.

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Pharmacodynamics
Bopindolol is a prodrug of pindolol. Pindolol is a non-selective beta-adrenergic antagonist (beta-blocker) which possesses intrinsic sympathomimetic activity (ISA) in therapeutic dosage ranges but does not possess quinidine-like membrane stabilizing activity. Pindolol impairs AV node conduction and decreases sinus rate and may also increase plasma triglycerides and decrease HDL-cholesterol levels. Pindolol is nonpolar and hydrophobic, with low to moderate lipid solubility. Pindolol has little to no intrinsic sympathomimetic activity and, unlike some other beta-adrenergic blocking agents, pindolol has little direct myocardial depressant activity and does not have an anesthetic-like membrane-stabilizing action.

C27H32N2O7

496.22

79125-22-7

Bopindolol;62658-63-3; 79125-22-7 (furamate); 82857-38-3 (malonate)

13302095

Typically exists as solid at room temperature

138

4

8

11

36

618

0

CC1=CC2=C(N1)C=CC=C2OCC(CNC(C)(C)C)OC(=O)C3=CC=CC=C3.C(=C/C(=O)O)\C(=O)O

SRGXLPJWUNBTKJ-WLHGVMLRSA-N

InChI=1S/C23H28N2O3.C4H4O4/c1-16-13-19-20(25-16)11-8-12-21(19)27-15-18(14-24-23(2,3)4)28-22(26)17-9-6-5-7-10-17;5-3(6)1-2-4(7)8/h5-13,18,24-25H,14-15H2,1-4H3;1-2H,(H,5,6)(H,7,8)/b;2-1+

(E)-but-2-enedioic acid;[1-(tert-butylamino)-3-[(2-methyl-1H-indol-4-yl)oxy]propan-2-yl] benzoate

Bopindolol fumarate; Sandonorm; 79125-22-7; Bopindolol (fumarate); UNII-GM76OF8LS3; GM76OF8LS3; 2-Propanol, 1-((1,1-dimethylethyl)amino)-3-((2-methyl-1H-indol-4-yl)oxy)-, benzoate (ester), (2E)-2-butenedioate (1:1) (salt); DTXSID101017990;

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。