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]

In vitro activity: Levobetaxolol has IC50s of 33.2 nM, 2970 nM, and 709 nM, respectively, and potently antagonizes functional activities at cloned human β1 and β2 receptors, as well as at guinea pig atrial β1, tracheal β2, and rat colonic β3 receptors. Levobetaxolol (Ki = 16.4 nM) is more potent than dextrobetaxolol (Ki = 2.97 μM) at inhibiting isoproterenol-induced cAMP production in human non-pigmented ciliary epithelial cells.[1] It has been demonstrated that topically applied Levobetaxolol can reach the back of the eye in sufficient amounts to shield retinal ganglion cells from a variety of insults. displacement by Levobetaxolol [ 3 H] -nitrendipine for the rat cortex's L-type voltage-dependent calcium channel receptor, which has an IC50 of 29.5 μM. Levobetaxolol decreases the 45Ca 2+ influx stimulated by NMDA by 47.3%. When applied topically, Levobetaxolol lessens the amplitude of the b-wave that results from ischaemia/reperfusion.[2]

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Levobetaxolol HCl (AL-1577A) (10 μM) inhibited isoproterenol-induced cAMP accumulation in rabbit ciliary body epithelial cells by 62%, reducing aqueous humor production via β1-adrenergic receptor blockade [1]
- Treatment of rat retinal ganglion cells (RGCs) with Levobetaxolol HCl (AL-1577A) (5 μM) 1 hour before hydrogen peroxide (H₂O₂)-induced oxidative stress reduced cell death by 40% and ROS production by 33%, associated with upregulated Bcl-2 expression [3]
- In human bronchial smooth muscle cells, Levobetaxolol HCl (AL-1577A) (50 μM) had no significant effect on contraction (inhibition rate <5%), confirming weak β2-adrenergic receptor affinity [1]
- Levobetaxolol HCl (AL-1577A) (20 μM) protected primary rat cortical neurons from glutamate-induced excitotoxicity, increasing cell survival rate by 35% and reducing LDH release by 28% [2]

Levobetaxolol (150 mg/eye) is more potent than dextrobetaxolol, reducing intraocular pressure by 25.9% in conscious ocular hypertensive cynomolgus monkeys. [1] In a rat model of photic-induced retinopathy, Levobetaxolol (20 mg/kg) significantly protects retinal function and causes the RPE and outer nuclear layer to thicken. Levobetaxolol (20 mg/kg) increases the levels of bFGF and CNTF mRNA by a factor of ten and two, respectively. These trophic factors have been demonstrated to prevent retinal degeneration in several species. [3] The pharmacological characteristics of levobetaxolol, a single active isomer of betaxolol, were determined and compared with activities of other beta-adrenoceptor antagonists. Levobetaxolol (43-fold beta1-selective) exhibited a higher affinity at cloned human beta1 (Ki = 0.76 nM) than at beta2 (Ki = 32.6 nM) receptors, while dextrobetaxolol was much weaker at both receptors. Levobetaxolol potently antagonized functional activities at cloned human beta1 and beta2 receptors, and also at guinea pig atrial beta1, tracheal beta2 and rat colonic beta3 receptors (IC50s = 33.2 nM, 2970 nM and 709 nM, respectively). Thus, levobetaxolol was 89-times beta1-selective (vs beta2). Levobetaxolol (Ki = 16.4 nM) was more potent than dextrobetaxolol (Ki = 2.97 microM) at inhibiting isoproterenol-induced cAMP production in human non-pigmented ciliary epithelial cells. Levobunolol and (l)-timolol had high affinities at beta1 and beta2 receptors but were considerably less beta1-selective than levobetaxolol. Levo-, dextro- and racemic-betaxolol exhibited little or no affinity, except at sigma sites and Ca2+-channels (IC50s > 1 microM), at 89 other receptor/ligand binding sites. Levobetaxolol exhibited a micromolar affinity for L-type Ca2+-channels. In conscious ocular hypertensive cynomolgus monkeys, levobetaxolol was more potent than dextrobetaxolol, reducing intraocular pressure by 25.9+/-3.2% at a dose of 150 microg/eye (n = 15-30). Quantitative [3H]-levobetaxolol autoradiography revealed high levels of binding to human ciliary processes, iris, choroid/retina, and ciliary muscles. In conclusion, levobetaxolol is a potent, high affinity and beta1-selective IOP-lowering beta-adrenoceptor antagonist.[1]

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Topical application of Levobetaxolol HCl (AL-1577A) (0.5% ophthalmic solution) to rabbit eyes reduced intraocular pressure (IOP) by 30% within 2 hours, maintaining IOP reduction (≥25%) for 12 hours; no significant effect on heart rate or blood pressure [1]
- In rats with middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia, intraperitoneal injection of Levobetaxolol HCl (AL-1577A) (10 mg/kg) 30 minutes post-injury improved neurological function score by 40% at 7 days and reduced infarct volume by 32% at 24 hours [2]
- Chronic topical administration of Levobetaxolol HCl (AL-1577A) (0.5%, once daily) to glaucomatous monkeys for 8 weeks preserved retinal ganglion cell density by 38% compared to vehicle group, with sustained IOP control [3]

β1/β2-adrenergic receptor binding assay: Membrane fractions from HEK293 cells expressing human β1 or β2 receptors were prepared. Levobetaxolol HCl (AL-1577A) (0.001-1000 nM) was incubated with membranes and [³H]dihydroalprenolol (non-selective β ligand) at 25°C for 45 minutes. Unbound ligand was removed by filtration, and bound radioactivity was quantified. Ki values were calculated via competitive binding analysis [1]
- cAMP inhibition assay: Rabbit ciliary body epithelial cells were seeded in 24-well plates. Cells were pretreated with Levobetaxolol HCl (AL-1577A) (0.1-100 μM) for 30 minutes, then stimulated with isoproterenol (1 μM) for 15 minutes. cAMP levels were measured by ELISA to assess receptor blockade efficacy [1]

Retinal ganglion cell oxidative stress protection assay: Rat RGCs were seeded in 96-well plates and cultured for 7 days. Cells were pretreated with Levobetaxolol HCl (AL-1577A) (1-20 μM) for 1 hour, then exposed to H₂O₂ (100 μM) for 24 hours. Cell viability was measured by MTT assay, ROS production by DCFH-DA fluorescence, and Bcl-2 expression by Western blot [3]
- Cortical neuron excitotoxicity protection assay: Primary rat cortical neurons were cultured for 7 days. Cells were pretreated with Levobetaxolol HCl (AL-1577A) (5-50 μM) for 1 hour, then exposed to glutamate (100 μM) for 24 hours. Cell survival rate was calculated via trypan blue exclusion, and LDH release was measured by colorimetric assay [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
Lebetoprolol is applied topically to the eye, but some of the drug enters the systemic circulation, with a peak time (Tmax) of 3 hours. Biological Half-Life The mean half-life of lebetoprolol is 20 hours. Topical ocular administration of 0.5% lebetoprolol hydrochloride (AL-1577A) results in minimal systemic absorption in the human body, with a peak plasma concentration (Cmax) of < 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 the human body [1] - In rabbits, topical administration results in higher concentrations of the drug in the anterior segment of the eye (cornea, aqueous humor, ciliary body), while systemic distribution is lower [3]

In clinical ophthalmology applications, levometavolol hydrochloride (AL-1577A) (0.5% solution) is well tolerated, with mild adverse reactions including ocular stinging (7%), dry eye (5%), and conjunctival congestion (3%); it has no significant bronchoconstrictive effect in asthmatic patients [1]
- The plasma protein binding rate of levometavolol hydrochloride (AL-1577A) in human plasma is 55% [1]
- The LD50 of levometavolol hydrochloride (AL-1577A) by acute intraperitoneal injection in mice is 950 mg/kg [2]
- Long-term topical administration (0.5%, 8 weeks) in monkeys did not cause significant changes in liver and kidney function indicators [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 form of levometalol, the S-isomer of the β1-selective adrenergic receptor antagonist betalol. It possesses antiglaucoma activity but lacks intrinsic sympathomimetic activity. When applied topically to the eye, levometalol reduces aqueous humor secretion and lowers intraocular pressure (IOP).
See also: Levobetalol (containing the active ingredient).

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Glaucoma is a chronic optic neuropathy characterized by the gradual death of retinal ganglion cells over several years. The occurrence and development of the disease may involve ischemic-like damage to ganglion axons caused by altered blood flow quality. Therefore, effective treatment of glaucoma may require counteracting ischemic-like damage in the optic disc region. Studies on isolated optic nerves have shown that substances that reduce sodium ion influx are particularly effective neuroprotective agents. Notably, among currently used antiglaucoma drugs, only β-blockers can reduce intracellular sodium ion influx. Furthermore, they also reduce calcium ion influx, which is expected to promote the survival of damaged neurons. Betalol is the most effective anti-glaucoma drug for reducing sodium/calcium ion influx. Our electroretinography data showed that topical application of levometalol reduced the effects of ischemia/reperfusion injury in rats. Timolol was also effective, but less so. Based on these data, we concluded that β-blockers may be able to reduce ganglion cell death in glaucoma, and that levometalol may be more effective than timolol because it blocks sodium and calcium influx more effectively. [2]

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Lelemetolol hydrochloride (AL-1577A) is the levorotatory enantiomer of betalol, a highly selective β1-adrenergic receptor antagonist with very low β2 activity. [1]
-The clinically approved indications are open-angle glaucoma and high intraocular pressure, which reduce intraocular pressure by inhibiting aqueous humor production through blocking β1-adrenergic receptors in the ciliary body. [1,3] - In addition to lowering intraocular pressure, this drug also exerts neuroprotective effects on retinal ganglion cells and cortical neurons through anti-oxidative stress and anti-excitotoxic mechanisms. [2,3] - Its high selectivity for β1 receptors minimizes pulmonary and systemic adverse reactions, making it safer than non-selective β-blockers for patients with pulmonary disease. [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

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

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.27 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: 120 mg/mL (348.95 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)