Timolol Maleate

(S)-Timolol maleate, is a potent non-selective β-adrenergic receptor antagonist (Ki values are 1.97 and 2.0 nM for β1 and β2 receptor subtypes respectively).

Sustained Delivery of Timolol Maleate for Over 90 Days by Subconjunctival Injection.[Pubmed:27835065]

J Ocul Pharmacol Ther. 2016 Dec;32(10):642-649.

PURPOSE: Medical treatment of glaucoma relies on intraocular pressure (IOP)-lowering medications, typically administered daily by the patient. While these medications are effective when applied correctly, patient adherence is a major obstacle in glaucoma treatment. We have developed a sustained-release formulation of Timolol Maleate that can be injected subconjunctivally to avoid patient noncompliance. METHODS: A biodegradable microsphere formulation for Timolol Maleate was injected subconjunctivally in normal rabbits. We measured timolol levels in tears, aqueous humor, vitreous humor, and serum of study rabbits. Furthermore, IOP profiles were recorded longitudinally. Tissue compatibility and side effects were evaluated using histochemistry. RESULTS: The microsphere formulation led to measureable amounts of timolol in the aqueous humor and the tear film for up to 90 days. Timolol was not detectable in the serum at any time. A significant reduction of IOP was observed in treated eyes. Clinically, the subconjunctival administration of the microspheres was well tolerated with no signs of inflammation or infection. The absence of local inflammation was confirmed by histology. CONCLUSIONS: A single subconjunctival administration of timolol microspheres achieved delivery and IOP reduction in rabbits for up to 90 days without local or systemic inflammation or toxicity. This approach has the potential to improve the management of glaucoma in patient populations, who are challenged to adhere to a regimen of daily eye drops.

Fixed combination of travoprost and timolol maleate reduces intraocular pressure in Japanese patients with primary open-angle glaucoma or ocular hypertension: analysis by prostaglandin analogue.[Pubmed:28053501]

Clin Ophthalmol. 2016 Dec 20;11:55-61.

BACKGROUND: We have shown a decrease in mean intraocular pressure (IOP) by switching to travoprost/timolol fixed combination (TTFC) in subjects receiving prostaglandin analogue (PGA) monotherapy and requiring additional medication in a previous report. For analyzing factors affecting IOP reduction, baseline IOP and preceding PGA were selected as statistically and clinically significant factors. In this report, we examine IOP-lowering effect and adverse drug reactions by preceding PGA. METHODS: Patients with primary open angle glaucoma or ocular hypertension who received monotherapy with one of four PGAs (travoprost, latanoprost, tafluprost, or bimatoprost) for at least 3 months at 26 institutions and were determined to require additional medication by their primary physician were included. IOP reduction and adverse events were examined at 4, 8, and 12 weeks for each of four PGAs after switching to TTFC. RESULTS: In total, 157 patients who could be followed up for at least 4 weeks after switching to TTFC were included in the efficacy analysis. Multiple regression analysis was performed, and baseline IOP and PGA were found to be significant factors to IOP reduction. IOP reduction at week 12, adjusted with the regression model, was -3.5, -1.8, and -1.4 mmHg in the tafluprost, latanoprost, and travoprost groups, whereas it was -0.5 mmHg in the bimatoprost group. Along with differences in baseline IOP between groups, an IOP-lowering effect of >1 mmHg was noted in the tafluprost, latanoprost, and travoprost groups after the switch. IOP was maintained at 13.8-14.8 mmHg throughout the follow-up period. No serious adverse events or noteworthy issues were observed in any group after the switch. CONCLUSION: Clinically significant IOP-reducing effects of TTFC were observed in the latanoprost, travoprost, and tafluprost groups when switching from each PGA monotherapy, while there were some differences in effects between groups, with minimal safety concerns.

A New UPLC Method with Chemometric Design-Optimization Approach for the Simultaneous Quantitation of Brimonidine Tartrate and Timolol Maleate in an Eye Drop Preparation.[Pubmed:27881494]

J Chromatogr Sci. 2017 Feb;55(2):154-161.

A new ultra-performance liquid chromatography (UPLC) with photodiode array was proposed for the quantitation of Brimonidine Tartrate (BRI) and Timolol Maleate (TIM) in eye drop using experimental design and optimization methodology. A 3(3) full factorial design was applied to uncover the effects of the selected factors and their interactions on the chromatographic response function for the optimization of experimental conditions in the development of a new UPLC method. As a result, the optimal chromatographic conditions giving a better separation and short analysis time were found to be 49.2 degrees C for column temperature; 0.38 mL/min for flow rate and 56.7 % (v/v) for 0.1 M CH3COOH used in mobile phase. The elution of BRI and TIM was reported as 0.508 and 0.652 min within a short runtime of 1.5 min, respectively. Calibration graphs for BRI and TIM were obtained by the regression of the concentration on the peak area, which was detected at 246 and 298 nm, respectively. The method validation was performed by the analysis of the synthetic mixtures, intra-day and inter-day samples and standard addition samples. This study shows that the optimized and validated UPLC method is very promising and available for the quantification of BRI and TIM in an eye drop formulation.

[Chinese expert consensus on the use of topical timolol maleate treatment of infantile hemangiomas].[Pubmed:28275803]

Shanghai Kou Qiang Yi Xue. 2016 Dec;25(6):744-747.

Non-selective beta-blocker propranolol has been proved by FDA as the first-line agent for infantile hemangioma (IH) with dramatic response. To reduce the side effects caused by systemic administration of propranolol, Timolol Maleate treatment has been increasingly used as an alternative to systemic beta-blockers and watchful waiting for many IH patients in recent years. However, the appropriate indications, drug dosage, dosing regimen, time for initiation, optimal duration, monitoring for side effects still remains controversial. To standardize the use of topical timolol in treating IH, avoid overtreatment or under-treatment, as well as minimize complications, a Chinese expert consensus on the use of topical timolol treatment of IH has been approved and written by a multidisciplinary experts group based on an up-to-date literature review and repeated discussion, which can be used to reduce inappropriate variations in clinical practice and to promote the delivery of high quality, evidence-based health care for IH patients.

Beta-adrenoceptor antagonist activities and binding affinities of timolol enantiomers in rat atria.[Pubmed:2573714]

J Pharm Pharmacol. 1989 Sep;41(9):649-50.

S-Timolol is an effective anti-glaucoma drug, but has potentially hazardous side effects. Recently, R-timolol, also, has been reported to be effective in lowering elevated intraocular pressure. In the present study, the beta-adrenoceptor antagonist activities and binding of R- and S-enantiomers of timolol have been examined on rat atrial preparations. The beta-antagonistic activities were investigated using spontaneously beating rat heart atria. Both timolol enantiomers inhibited (-)-isoprenaline-induced chronotropic action competitively. S-Timolol was about 54 times more potent than R-timolol. The apparent binding affinities of timolol enantiomers to beta 1- and beta 2-adrenoceptors were determined by a radioligand binding assay using (-)-[125I]iodocyanopindolol (ICYP) as a marker and CGP 20712 A as a beta 1- and ICI 118,551 as a beta 2-adrenoceptor antagonist. Both enantiomers of timolol inhibited ICYP binding in nanomolar concentrations with Hill coefficients near unity. Neither enantiomer showed selectivity between beta 1- and beta 2-adrenoceptors, but R-timolol was approximately 30 times less active than S-timolol. It is concluded that R-timolol is a relatively potent non-selective beta-adrenoceptor blocking agent, but may possibly exert a more localized beta-adrenoceptor action in the eye than S-timolol, thus improving the safety of ocular timolol therapy.

(S)-Timolol Maleate (L-714,465 Maleate) is a non-cardioselective hydrophilic β-adrenoceptor blocker. (S)-Timolol Maleate is widely used as standard medication for intraocular pressure (glaucoma) by preventing the production of aqueous humor. (S)-Timolol Maleate can be used for hypertension, angina pectoris and myocardial infarction.

Timolol Maleate,26921-17-5,Natural Products,Adrenergic Receptor, buy Timolol Maleate , Timolol Maleate supplier , purchase Timolol Maleate , Timolol Maleate cost , Timolol Maleate manufacturer , order Timolol Maleate , high purity Timolol Maleate