Betaxolol

Betaxolol is a cardioselective beta-adrenergic receptor blocking agent. Betaxolol (5 mg/kg via i.p. injection) was administered at 24 and then 44 h following the final chronic cocaine administration. Animals treated with betaxolol during cocaine withdrawa

Influence of Betaxolol on the Methamphetamine Dependence in Mice.[Pubmed:27247598]

Psychiatry Investig. 2016 May;13(3):316-20.

OBJECTIVE: The noradrenaline system is involved in the reward effects of various kinds of abused drugs. Betaxolol (BTX) is a highly selective beta1-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.

[Preservative-free betaxolol for POAG patients: evaluation of hypotensive effect and ocular surface safety].[Pubmed:26080587]

Vestn Oftalmol. 2015 Mar-Apr;131(2):76-80.

AIM: To evaluate ocular surface changes in patients with primary open-angle glaucoma (POAG) as well as the hypotensive effect of preservative-free Betaxolol eye drops. MATERIAL AND METHODS: A total of 22 patients (42 eyes) aged 55-83 with POAG stage I-II were examined. All of them were switched from Betaxolol b.i.d. to its preservative-free analogue (Xonef BK). The baseline examination included visual acuity measurement, Morisky-Green test (questionnaire), Norn test, Schirmer's test, lissamine green staining, and ocular tonometry. The latter was repeated 2 and 4 weeks after the drug had been switched, while the whole complex--2 months after the beginning of the study. RESULTS: The total tear production in POAG patients under Betaxolol therapy was 19.1 +/- 10.6 mm. After the 2 months of preservative-free Betaxolol use there were no statistically significant changes in Schirmer's test results (p = 0.248). Tear film break-up time (Norn test) improved from 7.8 +/- 0.5 secto 9.8 +/- 0.8 sec (p = 0.067) as well as the results of lissamine green staining (W = 90.0, p < 0.022). In the Morisky-Green Test Betaxolol patients scored only 2.6 +/- 0.05 points on average, thus showing non-compliance. After the 2 months of preservative-free Betaxolol instillations the scores increased up to 3.1 +/- 0.07 (p = 0.04). According to Dunnett's test, used for multiple comparisons, intraocular pressure did not change significantly in either of the study periods (baseline and follow-up measurements at weeks 2, 4, and 8 were taken into account). CONCLUSION: The study proves Xonef BK safe, effective, and appropriate in all types of glaucoma.

A novel ion-exchange carrier based upon liposome-encapsulated montmorillonite for ophthalmic delivery of betaxolol hydrochloride.[Pubmed:28280338]

Int J Nanomedicine. 2017 Mar 2;12:1731-1745.

As a novel ion-exchange carrier with high surface area and excellent exchangeability, montmorillonite (Mt) was intercalated with Betaxolol hydrochloride (BH) to form a nanocomposite and then encapsulated by liposomes (Mt-BH-LPs) for an ophthalmic drug-delivery system. The Mt-BH and Mt-BH-LPs were prepared by an acidification process and ethanol injection combined with ammonium sulfate gradient methods. The successful formation of Mt-BH and Mt-BH-LPs was verified by thermogravimetric analysis, X-ray diffraction, Fourier-transform infrared spectra, and transmission electron microscopy. Mt-BH-LPs possessed the favorable physical characteristics of encapsulation efficiency, drug loading, mean particle size, and zeta-potential. In vitro release studies indicated Mt-BH-LPs effectively maintained a relatively sustained slow release. Immortalized human corneal epithelial cell cytotoxicity, in vivo rabbit eye-irritation tests, and chorioallantoic membrane-trypan blue staining all revealed that Mt-BH-LPs had no obvious irritation on ocular tissues. A new in vitro tear-turnover model, including inserts containing human corneal epithelial cells, was designed to evaluate the precorneal retention time of Mt-BH-LPs. The results showed that Mt-BH-LPs maintained a certain BH concentration in tear fluid for a longer period than the BH solution. In vivo precorneal retention studies also indicated Mt-BH-LPs prolonged drug retention on the ocular surface more than the BH solution. Furthermore, pharmacodynamic studies showed that Mt-BH-LPs had a prolonged effect on decreasing intraocular optical pressure in rabbits. Our results demonstrated that Mt-BH-LPs have potential as an ophthalmic delivery system.

Preparation, pharmacokinetics and pharmacodynamics of ophthalmic thermosensitive in situ hydrogel of betaxolol hydrochloride.[Pubmed:27470557]

Biomed Pharmacother. 2016 Oct;83:107-113.

Conventional ophthalmic formulations often eliminate rapidly after administration and cannot provide and maintain an adequate concentration of the drug in the precorneal area. To solve those problems, a thermosensitive in situ gelling and mucoadhesive ophthalmic drug delivery system was prepared and evaluated, the system was composed of poloxamer analogs and polycarbophil (PCP) and Betaxolol hydrochloride (BH) was selected as model drug. The concentrations of poloxamer 407 (P407) (22% (w/v)) and poloxamer 188 (P188) (3.5% (w/v)) were identified through central composite design-response surface methodology (CCD-RSM). The BH in situ hydrogel (BH-HG) was liquid solution at low temperature and turned to semisolid at eye temperature. BH-HG showed good stability and biocompatibility, which fulfilled the requirements of ocular application. In vitro studies indicated that addition of PCP enhanced the viscosity of BH-HG and the release results of BH from BH-HG demonstrated a sustained release behavior of BH because of the gel dissolution. In vivo pharmacokinetics and pharmacodynamics studies indicated that the BH-HG formulation resulted in an improved bioavailability and a significantly lower intraocular pressure (IOP). The results suggested BH-HG could be potentially used as an in situ gelling system for ophthalmic delivery to enhance the bioavailability and efficacy.