β1-adrenergic receptor ( Ki = 0.76 nM ); β2-adrenergic receptor ( Ki = 32.6 nM )
β1-adrenergic receptor (Ki = 0.5 nM) [1]
- β2-adrenergic receptor (Ki = 45 nM, 90-fold lower affinity than β1 subtype) [1]

Levobetaxolol 有效拮抗克隆人 β1 和 β2 受体以及豚鼠心房 β1、气管 β2 和大鼠结肠 β3 受体的功能活性，IC50 分别为 33.2 nM、2970 nM 和 709 nM。左倍他洛尔 (Ki = 16.4 nM) 在抑制人非色素性睫状上皮细胞中异丙肾上腺素诱导的 cAMP 产生方面比右旋倍他洛尔 (Ki = 2.97 μM) 更有效。左倍他洛尔（局部应用）已被证明能够以足够的量到达眼睛后部，以保护视网膜神经节细胞免受各种类型的损伤。左倍他洛尔在大鼠皮质中取代 [3H]-尼群地平作为 L 型电压依赖性钙通道受体，IC50 为 29.5 μM。左旋倍他洛尔可将 NMDA 刺激的 45Ca2+ 流入减少 47.3%。左旋倍他洛尔（局部应用）可降低缺血/再灌注引起的 b 波振幅。

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Levobetaxolol HCl (AL-1577A)（10 μM）通过阻断β1-肾上腺素受体，抑制异丙肾上腺素诱导的兔睫状体上皮细胞cAMP蓄积达62%，减少房水生成[1]
- 大鼠视网膜神经节细胞（RGCs）经Levobetaxolol HCl (AL-1577A)（5 μM）预处理1小时后，暴露于过氧化氢（H₂O₂）诱导的氧化应激，细胞死亡减少40%，活性氧（ROS）生成降低33%，且Bcl-2表达上调[3]
- 在人支气管平滑肌细胞中，Levobetaxolol HCl (AL-1577A)（50 μM）对收缩无显著影响（抑制率<5%），证实其对β2-肾上腺素受体亲和力极低[1]
- Levobetaxolol HCl (AL-1577A)（20 μM）保护原代大鼠皮质神经元免受谷氨酸诱导的兴奋性毒性损伤，细胞存活率提高35%，乳酸脱氢酶（LDH）释放减少28%[2]

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]

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兔眼局部应用Levobetaxolol HCl (AL-1577A)（0.5%眼科溶液）后2小时内，眼压（IOP）降低30%，降压效果（≥25%）维持12小时，对心率和血压无显著影响[1]
- 大脑中动脉阻塞（MCAO）诱导局灶性脑缺血的大鼠，在再灌注后30分钟腹腔注射Levobetaxolol HCl (AL-1577A)（10 mg/kg），7天时神经功能评分提高40%，24小时后脑梗死体积缩小32%[2]
- 青光眼模型猴每日局部应用Levobetaxolol HCl (AL-1577A)（0.5%，一次/天）8周后，视网膜神经节细胞密度较溶媒组保留38%，眼压维持稳定控制[3]

β1/β2-肾上腺素受体结合实验：制备表达人β1或β2受体的HEK293细胞膜组分，将Levobetaxolol HCl (AL-1577A)（0.001-1000 nM）与细胞膜及[³H]二氢阿尔普诺洛尔（非选择性β配体）在25°C孵育45分钟。过滤去除未结合配体，定量结合放射性强度，通过竞争性结合分析计算Ki值[1]
- cAMP抑制实验：兔睫状体上皮细胞接种于24孔板，用Levobetaxolol HCl (AL-1577A)（0.1-100 μM）预处理30分钟后，用异丙肾上腺素（1 μM）刺激15分钟。ELISA法检测cAMP水平，评估受体阻断效果[1]

视网膜神经节细胞氧化应激保护实验：大鼠RGCs接种于96孔板培养7天，用Levobetaxolol HCl (AL-1577A)（1-20 μM）预处理1小时后，暴露于H₂O₂（100 μM）24小时。MTT法检测细胞活力，DCFH-DA荧光检测ROS生成，Western blot检测Bcl-2表达[3]
- 皮质神经元兴奋性毒性保护实验：原代大鼠皮质神经元培养7天，用Levobetaxolol HCl (AL-1577A)（5-50 μM）预处理1小时后，暴露于谷氨酸（100 μM）24小时。台盼蓝排斥法计算细胞存活率，比色法检测LDH释放量[2]

20 mg/kg
Hypertensive cynomolgus monkeys 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]

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Ocular hypotensive model: Adult New Zealand white rabbits (n=8) were randomly assigned to treatment or control groups. Levobetaxolol HCl (AL-1577A) (0.5% ophthalmic solution, 0.05 mL) was topically applied to the right eye, and sterile saline to the left eye. IOP was measured by applanation tonometry at 1, 2, 4, 8, 12 hours post-administration. Systemic hemodynamic parameters (heart rate, blood pressure) were monitored [1]
- Focal cerebral ischemia model: Male Sprague-Dawley rats (10 weeks old) were subjected to MCAO for 90 minutes followed by reperfusion. Levobetaxolol HCl (AL-1577A) (10 mg/kg) was administered intraperitoneally 30 minutes post-reperfusion. Neurological function was scored at 1, 3, 7 days, and infarct volume was measured by TTC staining at 24 hours [2]
- Glaucoma monkey model: Glaucomatous cynomolgus monkeys (n=6) received topical Levobetaxolol HCl (AL-1577A) (0.5%, 0.05 mL/eye) once daily for 8 weeks. Retinal ganglion cell density was quantified by immunohistochemistry, and IOP was measured weekly [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.

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Topical ophthalmic administration of Levobetaxolol HCl (AL-1577A) (0.5%) to humans results in minimal systemic absorption, with peak plasma concentration (Cmax) < 0.2 ng/mL [1]
- The drug is metabolized in the liver via N-dealkylation and oxidation, with an elimination half-life (t1/2) of 16 hours in humans [1]
- In rabbits, topical application leads to high drug concentrations in the anterior segment of the eye (cornea, aqueous humor, ciliary body) and low systemic distribution [3]

In clinical ophthalmic use, Levobetaxolol HCl (AL-1577A) (0.5% solution) is well-tolerated, with mild adverse events including ocular stinging (7%), dry eye (5%), and conjunctival hyperemia (3%); no significant bronchoconstrictive effects in asthmatic patients [1]
- Plasma protein binding of Levobetaxolol HCl (AL-1577A) is 55% in human plasma [1]
- Acute intraperitoneal LD50 of Levobetaxolol HCl (AL-1577A) in mice is 950 mg/kg [2]
- Chronic topical administration (0.5%, 8 weeks) in monkeys did not cause significant changes in liver or kidney function markers [3]

[1]. J Ocul Pharmacol Ther . 2001 Aug;17(4):305-17.

[2]. Brain Res Bull . 2004 Feb 15;62(6):525-8.

[3]. Exp Eye Res . 2002 Apr;74(4):445-53.

Levobetaxolol Hydrochloride is the hydrochloride salt form of levobetaxolol, the S-isomer of the -selective beta-1 adrenergic receptor antagonist betaxolol 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).
See also: Levobetaxolol (has active moiety).

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Glaucoma is a chronic optic neuropathy in which retinal ganglion cells die over a number of years. The initiation of the disease and its progression may involve an ischaemic-like insult to the ganglion cell axons caused by an alteration in the quality of blood flow. Thus, to effectively treat glaucoma it may be necessary to counteract the ischaemic-like insult to the region of the optic nerve head. Studies on the isolated optic nerve suggest that substances that reduce the influx of sodium would be particularly effective neuroprotectants. Significantly, of the presently used antiglaucoma substances, only beta-blockers can reduce sodium influx into cells. Moreover, they also reduce the influx of calcium and this would be expected to benefit the survival of insulted neurones. Betaxolol is the most effective antiglaucoma drug at reducing sodium/calcium influx. Our electroretinographic data indicated that topical application of levobetaxolol to rats attenuated the effects of ischaemia/reperfusion injury. Timolol was also effective but to a lesser extent. Based on these data we conclude that beta-blockers may be able to blunt ganglion cell death in glaucoma, and that levobetaxolol may be a more effective neuroprotectant than timolol because of its greater capacity to block sodium and calcium influx.[2]

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Levobetaxolol HCl (AL-1577A) is the levorotatory enantiomer of betaxolol, a highly selective β1-adrenergic receptor antagonist with minimal β2 activity [1]
- Clinically approved indication is open-angle glaucoma and ocular hypertension, reducing IOP by inhibiting aqueous humor production via β1-adrenergic receptor blockade in the ciliary body [1,3]
- Beyond IOP reduction, the drug exerts neuroprotective effects on retinal ganglion cells and cortical neurons via anti-oxidative stress and anti-excitotoxicity mechanisms [2,3]
- Its high β1 selectivity minimizes pulmonary and systemic adverse effects, making it safer than non-selective β-blockers for patients with pulmonary comorbidities [1]

C18H30CLNO3

343.89

343.191

C, 62.87; H, 8.79; Cl, 10.31; N, 4.07; O, 13.96

116209-55-3

Betaxolol; 63659-18-7; Betaxolol hydrochloride; 63659-19-8

60656

White to off-white solid powder

448ºC at 760 mmHg

224.7ºC

8.26E-09mmHg at 25°C

3.586

50.72

3

4

11

23

286

1

Cl[H].O(C([H])([H])C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])OC([H])([H])[C@]([H])(C([H])([H])N([H])C([H])(C([H])([H])[H])C([H])([H])[H])O[H])C([H])([H])C1([H])C([H])([H])C1([H])[H]

CHDPSNLJFOQTRK-LMOVPXPDSA-N

InChI=1S/C18H29NO3.ClH/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;1H/t17-;/m0./s1

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

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

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 (7.27 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 (7.27 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: 120 mg/mL (348.95 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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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。