Cellular cytotoxicity of antiglaucoma drugs in cultured corneal endothelial cells.

In this study, the various antiglaucoma drugs including betaxolol, timolol, levobunolol, carteolol, brimonidine, dipivefrin, dorzolamide, brinzolamide, latanoprost, unoprostone, and pilocarpine were used to investigate the effects of cellular cytotoxicity in cultured bovine corneal endothelial cells. After exposure to the drugs in three dilutions, 1/100, 1/1,000, and 1/10,000, for 100 minutes, cells were estimated based on the release assay of lactate dehydrogenase (LDH) enzyme. It was found that cellular LDH was significantly released in the medium only at 1/100th dilution of betaxolol, brimonidine, dorzolamide, dipivefrin, latanoprost and unoprostone to 130%, 123%, 145%, 157%, 128% and 237%, respectively, compared with controls upon exposure to drugs for 100 minutes. Moreover, benzalkonium chloride preservative at the concentrations ranging from 0.001 to 0.00001 mg/mL did not affect cellular LDH release in bovine corneal endothelial cells. These results indicate that high concentrations of antiglaucoma drugs may induce cytotoxicity in corneal endothelial cells.

The beta-1 adrenergic antagonist, betaxolol, improves working memory performance in rats and monkeys.

BACKGROUND: Previous studies have indicated that beta adrenergic receptor stimulation has no effect on the cognitive functioning of the prefrontal cortex (PFC). Blockade of beta-1 and beta-2 receptors in the PFC with the mixed beta-1/beta-2 antagonist, propanolol, had no effect on spatial working memory performance. However, more selective blockade of beta-1 or beta-2 receptors might show efficacy if the two receptors have opposite effects on PFC function. The current study examined the effects of the selective beta-1 antagonist, betaxolol, on working memory in rats and monkeys. METHODS: In rats, betaxolol (.0011-1.11 microg/.5 microL) was infused into the PFC 5 min before delayed alternation testing. Monkeys were systemically injected with betaxolol (.0000011-.11 mg/kg) 2 hours before delayed response testing. RESULTS: Betaxolol produced a dose-related improvement in working memory performance following either direct PFC infusion in rats, or systemic administration in monkeys. However, some aged monkeys developed serious pancreatic problems over the course of this study. CONCLUSIONS: These findings suggest that endogenous activation of the beta-1 adrenergic receptor impairs PFC cognitive function. These results may have therapeutic relevance to post-traumatic stress disorder or other disorders with excessive noradrenergic activity and PFC dysfunction. Pancreatic side effects in aged subjects taking betaxolol warrants further investigation.

The comparative cardiovascular, pulmonary, ocular blood flow, and ocular hypotensive effects of topical travoprost, bimatoprost, brimonidine, and betaxolol.

OBJECTIVE: This study evaluated systemic and ocular acute safety and intraocular pressure (IOP)-lowering efficacy of travoprost 0.004% and bimatoprost 0.03%, compared to brimonidine 0.2% and betaxolol 0.25% in healthy subjects. PATIENTS AND METHOD: Nineteen (19) young men, ages between 24 and 42, were enrolled in a single-center, institutional randomized, double-masked, crossover clinical trial. Baseline IOP, heart rate, blood pressure, and respiratory rate were recorded at hour 0. At minute 30, heart rate, blood pressure, respiratory rate, and spirometry were measured. At hour 1, color Doppler imaging of retrobulbar vessels was performed. At hour 2, heart rate, blood pressure, and respiratory rate were measured; spirometry and a 15-minute treadmill test were performed. The same protocol was applied after one drop of a study medication was instilled into each eye on four subsequent visits at 5-day intervals. RESULTS: Travoprost and bimatoprost did not cause significant reductions in systolic blood pressure during exercise and recovery. The mean respiratory rate and forced expiratory volume in 1 second were not significantly altered by any study medication. Travoprost reduced the resistive index and increased blood velocities in the ophthalmic artery and its branches. Bimatoprost caused a significant increase in end diastolic velocity of the ophthalmic artery. At hour 6, all medications reduced IOP significantly (p < 0.05). The most frequent ocular side effect of travoprost and bimatoprost was conjunctival hyperemia. CONCLUSION: Travoprost and bimatoprost were found to be systemically safe and caused an increase in blood-flow velocities of the retrobulbar vessels after a single-dose application. Their ocular hypotensive effect was comparable to that of brimonidine and greater than that of betaxolol in healthy subjects.

Ultrastructural effects of topical betoptic, betagan, and timoptic on the rabbit corneal endothelium.

Scanning and transmission electron microscopy was used to evaluate the cytotoxic effect of three commercially available beta adrenergic blockers (Betoptic 0.5%, Betagan 0.5% and Timoptic 0.5%), and preservative (benzalkonium chloride 0.01%) on rabbit corneal endothelium. Evaluation was performed on groups including intact corneas, de-epithelialized corneas, full-thickness corneal grafts with intact epithelium, and de-epithelialized corneal grafts. Both Betoptic and Betagan produced minor damage to endothelial microvilli in the intact epithelial group. The de-epithelialized and the grafted-cornea groups had less damage induced by Betoptic than Betagan. Timoptic produced more endothelial damage than Betoptic and Betagan in all groups. Benzalkonium chloride produced minimal endothelial damage. Results indicate that Betoptic produces less endothelial toxicity than the two non-specific beta blockers when corneal epithelium is damaged and after penetrating keratoplasty.