Neuroprotective Effects of Betaxolol Mediated by Heme Oxygenase-1 Induction in RGC-5

PURPOSE: To evaluate the neuroprotective effects of betaxolol (betaxolol hydrochloride) under hypoxic conditions using retinal ganglion cells (RGC-5) and determine whether heme oxygenase-1 (HO-1) expression exerts cytoprotective effects. METHODS: In this study, cultured RGC-5 cells were incubated with different concentrations of betaxolol hydrochloride (0.1 microM, 1 microM or 5 microM) and with 10 microM zinc protoporphyrin (ZnPP), in a hypoxia incubator (1% O2, 5% CO2, 94% N2) for 48 hours and the cell viability of each group was determined. Additionally, cell viability was measured after RGC-5 cells were incubated with 5 microM of brinzolamide (Azopt(R)), brimonidine tartrate (Alphagan(R)) or travoprost (Travatan(R)). RGC-5 cells were divided into three groups and incubated under three different conditions, normoxia group (20% O2, 5% CO2), hypoxia group (1% O2, 5% CO2) and the group with 5 microM of Betoptic S(R) treated under hypoxic conditions (hypoxia, Betoptic S(R)). After incubation for 4, 8, 12 and 24 hours, HO-1 expression was analyzed using Western blotting. RESULTS: Cell viability significantly increased in RGC-5 cells treated with Betoptic S(R) compared with other antiglaucoma agents. Increased levels of HO-1 expression indicate its relevance in cell viability. Furthermore, increased RGC-5 cell viability by Betoptic S(R) was significantly reduced in the HO-1 inhibitor ZnPP-treated group. CONCLUSIONS: We reaffirmed the known cytoprotective effects of Betoptic S(R) and the results suggests that HO-1 expression exerts cytoprotective effects against hypoxia.

Influence of Betaxolol on the Methamphetamine Dependence in Mice

OBJECTIVE: The noradrenaline system is involved in the reward effects of various kinds of abused drugs. Betaxolol (BTX) is a highly selective β1-antagonist. In the present study, we evaluated the effect of BTX on methamphetamine (MAP)-induced conditioned place preference (CPP) and hyperactivity in mice. METHODS: The mice (n=72) were treated with MAP or saline every other day for a total of 6 days (from day 3 to day 8; 3-times MAP and 3-times saline). Each mouse was given saline (1 mL/kg) or MAP (1 mg/kg, s.c.) or BTX (5 mg/kg, i.p.) or MAP with BTX (5 mg/kg, i.p.) 30 min prior to the administration of MAP (1 mg/kg, s.c.) every other day and paired with for 1 h (three-drug and three-saline sessions). We then compared the CPP score between the two groups. After the extinction of CPP, the mice were given BTX (5 mg/kg, i.p.) or saline (1 mL/kg) 24 h prior to a priming injection of MAP, and were then immediately tested to see whether the place preference was reinstated. RESULTS: The repeated administration of BTX 30 min prior to the exposure to MAP significantly reduced the development of MAP-induced CPP. When BTX was administered 24 h prior to the CPP-testing session on day 9, it also significantly attenuated the CPP, but did not result in any change of locomotor activity. In the drug-priming reinstatement study, the extinguished CPP was reinstated by a MAP (0.125 mg/kg, s.c.) injection and this was significantly attenuated by BTX. CONCLUSION: These findings suggest that BTX has a therapeutic and preventive effect on the development, expression, and drug-priming reinstatement of MAP-induced CPP.

Effects of Betaxolol Hydrochloride Cationic Liposomes on Intraocular Pressure, Blood Pressure and Heart Rate in Rabbits / 中国药师

Objective: To study the effects of betaxolol hydrochloride (BH) cationic liposomes on intraocular pressure (IOP), blood pressure ( BP) and heart rate ( HR) in rabbits to lay foundation for the development of new BH eye preparations. Methods:N-trimethyl chitosan (TMC60) was used as the coating material, the BH-loaded cationic liposomes (TMC60-BHL) were prepared. Total-ly 24 healthy rabbits were randomly divided into 4 groups using number method. Unilateral carotid artery intubation was carried out in the rabbits and connected a physiological recorder. TMC60-BHL, uncoated BHL, the marketed BH eye drops ( the positive control) and sterilized distilled water ( the negative control) with the volume of 50 μl was respectively used in one eye of the rabbits. IOP was detected by an ophthalmotonometer, and BP and HR were determined by the physiological recorder at the predetermined time intervals. Results:In the ipsilateral eyes, the maximum decrease in IOP for uncoated BHL and TMC60-BHL was 23. 00% and 26. 65%, respec-tively. In the contralateral eyes, the maximum decrease in IOP for uncoated BHL and TMC60-BHL was 18. 54% and 24. 33%, respec-tively. Compared with that of the positive control (19. 01%,15. 19%), the IOP decrease effect of uncoated BHL and TMC60-BHL was significant higher(P0. 05). Conclusion:TMC60-BHL shows significant IOP decrease effect without notable effect on BP and HR, which is valuable to be studied further.

Temperature Triggered In situ Gelling System for Betaxolol in Glaucoma.

The aim of this research is to develop thermo sensitive drug vehicles for glaucoma therapy in in-situ form to overcome the problems of poor bioavailability, naso lachrymal drainage and rapid precorneal elimination exhibited by conventional eye drops. Thermo sensitive ophthalmic drop was prepared using cold method by mixing thermo sensitive polymer pluronic F-127, viscosifying agent HPMC-E 50 LV and antiglaucoma drug (betaxolol hydrochloride). Prepared in situ gels were evaluated for physical parameters like appearance, gelation temperature, pH, drug content, rheological properties, isotonicity, sterility test, in vitro permeation and in-vivo ocular irritation study. The drug released from selected batch provides sustained release of betaxolol over 7 hours period and showed excellent ocular tolerance. The overall results of this study supports that the Pluronic/HPMC based vehicle could be used for controlled drug release that exhibits a greater potential for glaucoma therapy.

Desarrollo tecnológico de una formulación de betaxolol 0, 5 por ciento para administración oftálmica / Technological development of 0. 5 percent Betaxolol formulation for ophthalmological use

Introducción: el clorhidrato de betaxolol es un bloqueador cardioselectivo ß1 adrenérgico, que no presenta una actividad significativa como estabilizante de membrana (anestésico local) y carece de actividad simpaticomimética intrínseca. A nivel ocular actúa disminuyendo la producción de humor acuoso, reduciendo la presión intraocular a niveles normales, ya sea acompañada o no de glaucoma. Está indicado en el tratamiento del glaucoma crónico de ángulo abierto en pacientes con presión intraocular elevada (hipertensión ocular). Objetivo: diseñar una formulación de betaxolol 0,5 por ciento colirio, que cumpla con los índices de control de calidad para esta forma farmacéutica y que proporcione el efecto terapéutico deseado. Métodos: se realizaron cuatro variantes tecnológicas, modificando convenientemente las cantidades de excipientes y manteniendo la del principio activo, para lo que se tuvo en cuenta la composición de la formulación líder, con la finalidad de seleccionar la de mejor estabilidad en 3 meses de seguimiento. Se ajustó el pH y la isotonicidad de la formulación, según las exigencias de un preparado oftálmico. La isotonicidad se alcanzó con cloruro de sodio. Resultados: el desarrollo tecnológico de la formulación resultó satisfactorio, y se obtuvo un producto que cumplió con todas las especificaciones descritas en la USP 30, para el control de la calidad del producto. La preparación mantuvo sus propiedades físicas, químicas y microbiológicas inalterables por un período de 24 meses, almacenada a una temperatura de 30,0 ± 2,0 °C. Conclusiones: la formulación de un medicamento obtenida en forma de colirio que contiene betaxolol clorhidrato como principio activo para el tratamiento del glaucoma, cumple con todas las especificaciones de calidad para este tipo de forma farmacéutica, lo cual puede aumentar el arsenal terapéutico de Cuba

Introduction: Betaxolol chlorhydrate is a cardioselective adrenergic ß1 blocker that does not play a significant role as membrane stabilizer (local anesthestic) and lacks intrinsic sympathomimetic activity. It diminishes the production of aqueous humor in the eye, thus reducing the intraocular pressure to normal, either with or without glaucoma. This drug is indicated in the treatment of chronic open angle glaucoma affecting patients with ocular hypertension. Objective: to design a formulation of 0.5 por ciento Betaxolol eye drops that meets the quality control parameters for this pharmaceutical form and that provides the desired therapeutic effect. Methods: four technological variants were performed by adequately modifying the excipient quantities and by keeping the active principle amount, for which the composition of the leading formulation was taken into account. The aim was to select the most stable variant after 3-month follow-up. The pH and the isotonicity of the formulation were adjusted for the requirements of an ophthalmologic preparation. The isotonicity was reached with sodium chloride. Results: the technological development of this formulation was satisfactory; the final product met all the specifications for the quality control of the product as described in USP 30. The physical, chemical and microbiological properties of the preparation remained unchanged for 24 months under storage conditions of 30.0 ± 2.0 °C. Conclusions: the formulation of a medical eye drops containing Betaxolol chlorhydrate as active principle, meets all the quality specifications for this pharmaceutical form to treat glaucoma, which may expand the therapeutic options in Cuba

Comparative Effect of Timolol, Levobunolol and Betaxolol on IOP in Patients of Chronic Simple Glaucoma

In this prospective randomized parallel study we compared the effects of topical timolol maleate, levobunolol hydrochloride and betaxolol hydrochloride on intraocular pressure (IOP) in the patients of primary open angle glaucoma after 16 weeks of instillation as 1 drop 12 hourly in 0.5% concentration. 23 eyes of 16, 19 eyes of 12 and 20 eyes of 12 patients were included in timolol, levobunolol and betaxolol groups respectively. Timolol, levobunolol and betaxolol lowered IOP by 13.05 ± 1.53, 14.05 ±1.47 and 7.58 ± 0.90mmof Hg respectively after 6weeks and by16.12±1.67,16.28 ±1.85 and 8.535 ± 0.983 mm of Hg respectively after 16 weeks (P<0.001). Both levobunolol and timolol produced greater reduction in IOP than betaxolol (P<0.001). The results of our study indicated that betaxolol is less efficacious in lowering IOP in Indian patients and could only be preferred over timolol in glaucoma patients with associated chronic obstructed pulmonary disease (COPD) or bronchial asthma. However, Levobunolol could be a better alternative to timolol , as being a longer acting agent with IOP control for 24 hrs after single instillation and can be used as once a day instillation with better safety profile.

Protective effect of betaxolol on optic nerves after experimental retinal ischemia-reperfusion injury / 中华眼底病杂志

Objective To investigate the protective effect and mechanism of betaxolol on optic nerves after experimental retinal ischemia-reperfused injury. Methods Retinal ischemia was induced in SD rats by increasing intraocular pressure through intracameral infusion. Sixty-eight rats were randomly divided into 3 groups: normal control (eight rats), 0.25% betaxolol treatment (thirty rats) and saline control group (thirty rats). The latter two groups were subdivided into group 1 day, 3 and 7 days after reperfusion, respectively, with 10 rats in each group. Betaxolol and normal saline was applied to the right eyes of the rats in the treatment group and to the ones in normal saline control group, respectively. The amplitude of b-wave of electron retinograph (ERG) was observed and the histological and ultrastructural changes were detected by light and electron microscopy. The expression of neural nitrogen oxide synthase (nNOS) was detected by immunohistochemistry. The content of malonyldialdehyde (MDA) and the superoxide dismutase (SOD) activity were measured by spectrophotometer. Results [WTBZ]Began from the first day after reperfusion, in saline control group, the amplitudes of ERG b-wave reduced continuously, the histopathological damages of retina were aggravating, the expression of nNOS increased, MDA level increased and SOD level decreased persistently, which significantly differed from the normal control group (P0.01). Conclusion Betaxolol, by reducing intracellular overfreight of Ca~(2+),inhibiting production of NO and elevating the ability of anti-oxidation in rat retina, can protect retinal neurons from ischemia-reperfused injury.