Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new alphagan research articles will be listed here shortly after becoming available to us.
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Medical research on alphagan
Invest Ophthalmol Vis Sci. 2008 Jun 19;
Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA
Purpose. alpha2 agonists, such as brimonidine, have been shown to protect retinal ganglion cells (RGCs) in animal models of glaucoma and acute retinal ischemia. In this study, we investigated the neural mechanism that may underlie alpha2 neuroprotection of RGCs. Methods. We used in situ RGCs in the isolated rat retina to investigate possible interactions between alpha2 and NMDA (N-methyl-D-aspartate) receptors, and rat glaucoma or rabbit retinal NMDA excitotoxicity models to verify our in vitro findings under in vivo conditions. Results. Application of NMDA elicited a robust intracellular Ca++ signal and inward current in individual in situ RGCs voltage clamped at -70 mV. The NMDA-elicited responses were blocked by D-AP5 (D-2-Amino-5-phosphonopentanoic acid), a selective NMDA receptor antagonist. Brimonidine pretreatment also reduced significantly NMDA-elicited whole-cell currents and cytosolic Ca++ signals in RGCs. This suppressive action of brimonidine was blocked by alpha2 antagonists, cAMP analogs, an adenylate cyclase activator, and a cAMP-specific phosphodiesterase (PDE4) inhibitor, indicating that this brimonidine effect is mediated by the alpha2 receptor through a reduction of intracellular cAMP production. Brimonidine or NMDA receptor blockers protected RGCs in both rat glaucoma and rabbit retinal NMDA excitotoxicity models. The brimonidine neuroprotective effect was abolished by either an alpha2 antagonist or a PDE4 inhibitor in both in vivo models. Conclusions. Our results demonstrate alpha2 modulation of NMDA receptor function as an important mechanism for neuroprotection. These results suggest a new therapeutic approach based on neuromodulation, instead of direct inhibition, of the NMDA receptor for the treatment of glaucoma and other CNS disorders associated with NMDA receptor overactivation.
Curr Med Res Opin. 2008 Jun 4;
Cantor LB, Safyan E, Liu CC, Batoosingh AL
OBJECTIVE: To compare the safety and intraocular pressure (IOP)-lowering effects of brimonidine-purite 0.1% with the marketed formulation of brimonidine-purite 0.15% (Alphagan P 0.15%) when used twice daily (BID) by patients with glaucoma or ocular hypertension previously treated with brimonidine-purite 0.15% for at least 6 weeks. METHODS: In a 12-month, randomized, double-masked, multicenter, parallel group, non-inferiority study, patients with glaucoma or ocular hypertension who were treated with brimonidine-purite 0.15% BID were randomly assigned to continue brimonidine-purite 0.15% (n = 102) or to administer brimonidine-purite 0.1% (n = 105) BID for 12 months. IOP was measured at approximately 8 a.m. (hour 0) and 10 a.m. (hour 2). MAIN OUTCOME MEASURES: Mean change from baseline IOP and adverse events. RESULTS: Demographics and baseline characteristics were similar between treatment groups. Treated-baseline mean IOPs at both timepoints were similar between groups ( p >/= 0.606). Brimonidine-purite 0.1% provided IOP-lowering that was non-inferior to brimonidine-purite 0.15% at each of the 12 follow-up timepoints, and there were no statistically significant between-group differences at any timepoint. The most commonly reported adverse event was conjunctival hyperemia (13.5% for brimonidine-purite 0.1%; 10.8% for brimonidine-purite 0.15%). No significant differences in the incidence of adverse events were noted between the two formulations. CONCLUSIONS: Brimonidine-purite 0.1% BID is as effective as brimonidine-purite 0.15% BID in lowering IOP in patients with glaucoma or ocular hypertension who were previously treated with brimonidine-purite 0.15%, and both formulations are well tolerated. Limitations of the study include enrollment of only patients who were already on treatment with brimonidine-purite 0.15%. The 0.1% formulation of brimonidine-purite allows for decreased exposure to brimonidine while providing an IOP-lowering effect comparable to that of the 0.15% formulation. Clinical trial registered at clinicaltrials.gov; identifier: NCT00168363.
J Cataract Refract Surg. 2008 Jun; 34(6): 963-7
Lee JH, You YS, Choe CM, Lee ES
PURPOSE: To quantitatively evaluate the effect of brimonidine tartrate 0.2% (Alphagan) on halo and pupil size in patients who had symptomatic night-vision difficulties after laser in situ keratomileusis (LASIK). SETTING: Nune Eye Hospital, Seoul, Korea. METHODS: This study comprised 28 eyes of 14 patients with symptomatic night-vision difficulties after LASIK. Pupil diameter was measured with a Colvard pupillometer (Oasis Medical, Inc.). Quantitative analysis of halos was performed by measuring the area using a new computerized method. Pupil size and halo size were evaluated under scotopic and normal room light conditions. Alphagan was administered, and the effect was measured after 30 minutes and 1, 6, 12, and 24 hours. RESULTS: There was a statistically significant correlation between pupil size and halo size (r = 0.527; P
J Ocul Pharmacol Ther. 2008 Jun; 24(3): 364-5; author reply 366
Khanani AM, Brown SM
Clin Experiment Ophthalmol. 2008 Apr; 36(3): 281-9
Loon SC, Liew G, Fung A, Reid SE, Craig JC
This paper aims to compare the efficacy and tolerability of timolol versus brimonidine in the treatment of glaucoma. Comprehensive searches were performed using Medline, Embase and the Cochrane Controlled Trials Register for randomized controlled trials comparing timolol and brimonidine. Two reviewers independently assessed trials for eligibility and quality and extracted data. A random effects model was used to combine studies. Outcome was defined as the absolute mean intraocular pressure (IOP) reduction from baseline to end-point for efficacy, and relative risk (RR) for adverse events. Subgroup analysis and meta-regression were used to explore heterogeneity according to trial design and quality. Ten publications reporting on eight trials with 2387 participants were included in the meta-analysis. Two further trials were commented on qualitatively. IOP reduction was not significantly different between timolol and brimonidine. Weighted mean difference (WMD) of IOP reduction was 0.24 mmHg (favouring brimonidine) with a 95% confidence interval of -0.57 to 1.04 mmHg. There was significant heterogeneity between studies (chi(2) (13) = 73.75, P < 0.00001, I(2) = 91%). Subgroup analysis showed no significant WMD for studies where data were analysed from end-points >/=6 months or
Curr Med Res Opin. 2008 May; 24(5): 1435-42
Day DG, Hollander DA
OBJECTIVE: To evaluate the efficacy and tolerability of brimonidine purite 0.1% in comparison to brinzolamide 1% when used as adjunctive therapy to latanoprost 0.005% in patients with glaucoma or ocular hypertension. METHODS: Randomized, single-center, investigator-masked, parallel-group clinical study. Patients with IOP >or= 18 mmHg while on once-daily latanoprost were randomized to adjunctive treatment with brimonidine purite TID (n = 20) or brinzolamide TID (n = 20) for 3 months. Intraocular pressure (IOP) was measured at 8 a.m., 10 a.m., and 4 p.m. at latanoprost-treated baseline and after 1 and 3 months of latanoprost and adjunctive therapy. A patient questionnaire was administered to evaluate the tolerability of eye drop instillation. RESULTS: Baseline mean diurnal IOP (+/- standard deviation, mmHg) on latanoprost was comparable between groups (brimonidine purite: 19.6 +/- 2.94; brinzolamide: 19.8 +/- 3.25; p = 0.846). Mean diurnal IOP at Month 3 was 16.3 +/- 2.63 mmHg with brimonidine purite and 17.8 +/- 2.19 mmHg with brinzolamide (p = 0.028). Adjunctive use of brimonidine purite provided greater IOP lowering than brinzolamide at 10 a.m. (p < 0.001) and 4 p.m. (p = 0.050) and equivalent IOP lowering to brinzolamide at 8 a.m. (p = 0.716). Blurred vision at Month 1 and bitter taste at Months 1 and 3 were more common upon instillation of brinzolamide eye drops. CONCLUSION: Brimonidine purite 0.1% provided significantly lower IOP compared with brinzolamide 1% when used as adjunctive therapy to latanoprost. Both adjunctive therapies were well tolerated. Limitations of this study include the use of a single site and the sample size. Additional studies are needed to further evaluate these drugs as adjunctive therapy to prostaglandin analogs.
Exp Eye Res. 2008 May; 86(5): 798-806
Hernández M, Urcola JH, Vecino E
The aim of the present study is to evaluate the neuroprotective effect of two antiglaucomatous substances, regardless of their hypotensive effect in the eye. Brimonidine, which does not reduce IOP when administered intraperitoneally, and latanoprost, which has a renowned hypotensive effect topically. We examined rat retinal ganglion cell (RGC) survival and size distribution in experimental glaucoma in response to different glaucomatous agents. IOP was elevated by episcleral vein cauterization (EVC) prior to the application of different treatments: (I) PBS application (control group), (II) intraperitoneal administration of brimonidine (a general hypotensive agent), (III) topical application of latanoprost (an ocular hypotensive agent), and (IV) latanoprost combined with brimonidine. After 12 weeks, RGCs were retrogradely labeled with fluorogold and RGC density was analyzed. EVC caused a significant increase (42%) in IOP in each group before drug treatment. After 12weeks of EVC, RGC survival in control vs. EVC rats was 78.9+/-3.2%. No IOP reduction was observed in brimonidine injected rats, but RGC survival at 12 weeks was total (103.7+/-2.7%). In latanoprost treated rats, IOP dropped by around 22% and 94.7+/-3.7% of the RGC population survived. Finally in the latanoprost+brimonidine combined group, IOP was significantly reduced by 25% and 94.4+/-2.2% of RGCs survived. Surprisingly, whereas EVC led to a 6% increase in RGC soma size, brimonidine treatment was associated with a 9% reduction in the soma size of RGCs at 12 weeks. We conclude that brimonidine exerts a neuroprotective effect via a mechanism which is independent of IOP reduction. These findings indicate that cell survival in glaucoma may be enhanced by neuroprotective strategies which are independent of IOP reduction. No synergistic neuroprotective effect was observed when both treatments were applied simultaneously.
Brimonidine in the treatment of glaucoma and ocular hypertension.
Ther Clin Risk Manag. 2006 Dec; 2(4): 337-46
Cantor LB
Treatment in glaucoma aims to lower intraocular pressure (IOP) to reduce the risk of progression and vision loss. The alpha2-adrenergic receptor agonist brimonidine effectively lowers IOP and is useful as monotherapy, adjunctive therapy, and replacement therapy in open-angle glaucoma and ocular hypertension. A fixed combination of brimonidine and timolol, available in some countries, reduces IOP as effectively as concomitant therapy with brimonidine and timolol and offers the convenience of 2 drugs in a single eyedrop. Brimonidine is safe and well tolerated. Its most common side-effects are conjunctival hyperemia, allergic conjunctivitis, and ocular pruritus. The newest formulation of brimonidine, brimonidine-Purite 0.1%, has a higher pH to improve the ocular bioavailability of brimonidine. This formulation contains the lowest effective concentration of brimonidine and is preserved with Purite(R) to enhance ocular tolerability. Brimonidine-Purite 0.1% is as effective in reducing IOP as the original brimonidine 0.2% solution preserved with benzalkonium chloride. Recent results from preclinical and clinical studies suggest that brimonidine may protect retinal ganglion cells and their projections from damage and death independently of its effects on IOP. The potential for neuroprotection with brimonidine is an added benefit of its use in glaucoma and ocular hypertension.
Central alpha-2 adrenergic eye drops: case series of 3 pediatric systemic poisonings.
Pediatr Emerg Care. 2008 Mar; 24(3): 167-9
Rangan C, Everson G, Cantrell FL
Three pediatric patients presented with systemic central alpha-2 agonist poisoning-2 cases of bradycardia and apnea resulting from ingestion of ingestion of apraclonidine, with 1 case requiring intubation, and 1 case of bradycardia and altered mental status requiring intensive care monitoring resulting from therapeutic ophthalmic application of brimonidine. Pediatric poisonings involving central alpha-2 adrenergic agonists have been well described, particularly with the prototypical agent clonidine. Characteristic symptoms include sympatholytic effects such as central nervous system depression, respiratory depression, hypotension, bradycardia, miosis, hypothermia, and hyporeflexia. Although structurally similar to clonidine, these compounds are presumed to be safer for pediatric use because they are more polar and less lipophilic than clonidine, thereby limiting their ability to cross the blood-brain barrier and reducing incidence of centrally mediated effects. Systemic toxicities of alpha-2 agonist ophthalmic preparations in pediatric patients are similar to those seen with clonidine poisonings. Symptomatic patients should be treated in the same manner as patients with clonidine poisoning. Treatment of systemic poisoning is primarily supportive. Periodic tactile stimulation seems to be an effective nonpharmacological intervention to improve alpha-2 adrenergic agonist-induced central nervous system depression and respiratory depression. Intubation should be considered when tactile stimulation is not effective.
Effects of central corneal thickness on the efficacy of topical ocular hypotensive medications.
J Glaucoma. 2008 Mar; 17(2): 89-99
Johnson TV, Toris CB, Fan S, Camras CB
PURPOSE: To determine the effect of central corneal thickness (CCT) on the efficacy of intraocular pressure (IOP)-reducing drugs in patients with ocular hypertension (OHT). METHODS: This retrospective study analyzed research records of 115 OHT patients and 97 ocular normotensive (ONT) volunteers. CCT was measured by slit-lamp pachymetry and IOP by pneumatonometry. The OHT patients were divided into Thick (>540 microm, n=52) and Thin (