β1-adrenergic receptor ( Ki = 0.76 nM ); β2-adrenergic receptor ( Ki = 32.6 nM )

左倍他洛尔对克隆的人 β1 和 β2 受体具有更高的亲和力，Ki 值分别为 0.76 和 32.6 nM [1]。左旋倍他洛尔的 Kb 值分别为 6 和 39 nM，可抑制表达人重组 β1 和 β2 受体的细胞的功能活性 [1]。

左倍他洛尔（150 mg/眼）比右旋倍他洛尔更有效，可将清醒的高眼压食蟹猴的眼内压降低 25.9%。 Levobetaxolol (20 mg/kg) 可显着保护视网膜功能，并导致光诱导的视网膜病变大鼠模型中 RPE 和外核层显着增厚。 Levobetaxolol (20 mg/kg) 导致 bFGF 上调 10 倍，CNTF mRNA 水平上调两倍，这些营养因子已被证明可以抑制许多物种的视网膜变性。

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测定了左倍他洛尔的药理学特征，并将其与其他β肾上腺素受体拮抗剂的活性进行了比较。左贝他洛尔（β1选择性的43倍）对克隆的人β1（Ki=0.76 nM）受体的亲和力高于β2（Ki=32.6 nM），而右贝他洛尔对这两种受体的亲和力要弱得多。左旋紫杉醇能有效拮抗克隆的人β1和β2受体的功能活性，也能拮抗豚鼠心房β1、气管β2和大鼠结肠β3受体的功能活动（IC50分别为33.2 nM、2970 nM和709 nM）。因此，左倍他洛尔的β1选择性是β2的89倍。在抑制异丙肾上腺素诱导的人非色素睫状上皮细胞中cAMP的产生方面，左炔诺洛尔（Ki=16.4 nM）比右倍他洛尔（Ki=2.97 microM）更有效。左丁醇和（1）-噻吗洛尔对β1和β2受体具有高度亲和力，但β1选择性明显低于左倍他洛尔。左旋、右旋和外消旋倍他洛尔除了在σ位点和Ca2+通道（IC50＞1微M）以及89个其他受体/配体结合位点外，几乎没有亲和力。左替洛尔对L型Ca2+通道表现出微摩尔的亲和力。在清醒的眼高血压食蟹猴中，左倍他洛尔比右倍他洛尔更有效，在150微克/只眼睛的剂量下将眼压降低了25.9+/-3.2%（n=15-30）。定量[3H]-左倍他洛尔放射自显影显示，其与人类睫状突、虹膜、脉络膜/视网膜和睫状肌的结合水平很高。总之，左倍他洛尔是一种强效、高亲和力和β1选择性的降眼压β肾上腺素受体拮抗剂。[1]

Rats were dosed (IP) with vehicle or levobetaxolol (10 and 20 mg kg(-1)) 48, 24 and 0 hr prior to exposure for 6 hr to fluorescent blue light. The electroretinogram (ERG) and retinal morphology were assessed after a 3 week recovery period. Evaluation of the ERG demonstrated significant protection of retinal function in levobetaxolol (20 mg kg(-1))-dosed rats compared to vehicle-dosed rats. Similarly, the RPE and outer nuclear layer were significantly thicker in levobetaxolol (20 mg kg(-1))-dosed rats compared to vehicle-dosed rats. To elucidate potential mechanism(s) of the neuroprotective activity of levobetaxolol, bFGF and CNTF mRNA levels in normal rat retinas were evaluated 12 hr after a single i.p. injection. Northern blot analysis of levobetaxolol treated retinas demonstrated a 10-fold up-regulation of bFGF and a two-fold up-regulation of CNTF mRNA levels, trophic factors that have been shown to inhibit retinal degeneration in a number of species. These studies suggest that levobetaxolol can be used as a novel neuroprotective agent to ameliorate retinopathy.[3]

Absorption, Distribution and Excretion
Levobetaxolol is applied topically to the eye but some does reach systemic circulaton with a Tmax of 3 h.

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Biological Half-Life
The mean half life of levobetaxolol is 20 h.

[1]. Sharif NA, et al. Levobetaxolol (Betaxon) and other beta-adrenergic antagonists: preclinical pharmacology, IOP-lowering activity and sites of action in human eyes. J Ocul Pharmacol Ther. 2001 Aug;17(4):305-17.
[2]. Osborne NN, et al. Effectiveness of levobetaxolol and timolol at blunting retinal ischaemia is related to their calcium and sodium blocking activities: relevance to glaucoma. Brain Res Bull. 2004 Feb 15;62(6):525-8.

(S)-betaxolol is the (S)-enantiomer of betaxolol. It is an enantiomer of a (R)-betaxolol.
Levobetaxolol is a beta-blocker used to lower the pressure in the eye to treat conditions such as glaucoma. It was marketed as a 0.5% ophthalmic solution of levobetaxolol hydrochloride under the trade name Betaxon but has been discontinued.
Levobetaxolol is the S-isomer of betaxolol, a selective beta-1 adrenergic receptor antagonist with anti-glaucoma activity and devoid of intrinsic sympathomimetic activity. When applied topically in the eye, levobetaxolol reduces aqueous humor secretion and lowers the intraocular pressure (IOP).

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Drug Indication
Used in the treatment of open-angle glaucoma and ocular hypertension.
FDA Label

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Mechanism of Action
The exact mechanism by which levobetaxolol lowers intraocular pressure is not known. It it thought that antagonism of β-adrenergic receptors may reduce the production of aqueous humour stimulated via the cyclic adenosine monophosphate-protein kinase A pathway. It is also thought that the vasoconstriction produced by antagonism of β adrenergic receptors reduces blood flow to the eye and therefore the ultrafiltration responsible for aqueous humour production. β1 selective antagonists are less effective than non-selective β adrenergic receptor antagonists because β2 receptors make up the bulk of the population in the eye. They do, however, come with the benefit of reduced respiratory complications.

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Pharmacodynamics
Levobetaxolol is a selective β1 adrenergic receptor antagonist. It acts to lower intraocular pressure. Levobataxolol is condsidered to be the more active component of the betaxolol racemate.

C18H29NO3

307.43

307.215

93221-48-8

116209-55-3 (HCl); 93221-48-8; Betaxolol hydrochloride; 63659-19-8; Levobetaxolol hydrochloride; 116209-55-3; Betaxolol-d5; 1189957-99-0; 63659-18-7; 93221-48-8 (S-isomer free base); 116209-55-3 (S-isomer HCl)

60657

Typically exists as solid at room temperature

1.067g/cm3

448ºC at 760 mmHg

71-72ºC

224.7ºC

1.529

2.784

50.72

2

4

11

22

286

1

CC(C)NC[C@@H](COC1=CC=C(C=C1)CCOCC2CC2)O

NWIUTZDMDHAVTP-KRWDZBQOSA-N

InChI=1S/C18H29NO3/c1-14(2)19-11-17(20)13-22-18-7-5-15(6-8-18)9-10-21-12-16-3-4-16/h5-8,14,16-17,19-20H,3-4,9-13H2,1-2H3/t17-/m0/s1

(2S)-1-[4-[2-(cyclopropylmethoxy)ethyl]phenoxy]-3-(propan-2-ylamino)propan-2-ol

Levobetaxolol; (S)-Betaxolol; Levobetaxolol; (S)-Betaxolol; 93221-48-8; (-)-Betaxolol; (S)-(-)-Betaxolol; Levobetaxolol [INN]; Betaxolol, (s)-; (2S)-1-[4-[2-(cyclopropylmethoxy)ethyl]phenoxy]-3-(propan-2-ylamino)propan-2-ol; (S)-(-)-Betaxolol

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。