The carbonic anhydrase inhibitor methazolamide prevents amyloid beta-induced mitochondrial dysfunction and caspase activation protecting neuronal and glial cells in vitro and in the mouse brain.

Mitochondrial dysfunction has been recognized as an early event in Alzheimer's disease (AD) pathology, preceding and inducing neurodegeneration and memory loss. The presence of cytochrome c (CytC) released from the mitochondria into the cytoplasm is often detected after acute or chronic neurodegenerative insults, including AD. The carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) was identified among a library of drugs as an inhibitor of CytC release and proved to be neuroprotective in Huntington's disease and stroke models. Here, using neuronal and glial cell cultures, in addition to an acute model of amyloid beta (Aß) toxicity, which replicates by intra-hippocampal injection the consequences of interstitial and cellular accumulation of Aß, we analyzed the effects of MTZ on neuronal and glial degeneration induced by the Alzheimer's amyloid. MTZ prevented DNA fragmentation, CytC release and activation of caspase 9 and caspase 3 induced by Aß in neuronal and glial cells in culture through the inhibition of mitochondrial hydrogen peroxide production. Moreover, intraperitoneal administration of MTZ prevented neurodegeneration induced by intra-hippocampal Aß injection in the mouse brain and was effective at reducing caspase 3 activation in neurons and microglia in the area surrounding the injection site. Our results, delineating the molecular mechanism of action of MTZ against Aß-mediated mitochondrial dysfunction and caspase activation, and demonstrating its efficiency in a model of acute amyloid-mediated toxicity, provide the first combined in vitro and in vivo evidence supporting the potential of a new therapy employing FDA-approved CAIs in AD.

Optimization of methazolamide-loaded solid lipid nanoparticles for ophthalmic delivery using Box-Behnken design.

The purpose of the present study was to optimize methazolamide (MTZ)-loaded solid lipid nanoparticles (SLNs) which were used as topical eye drops by evaluating the relationship between design factors and experimental data. A three factor, three-level Box-Behnken design (BBD) was used for the optimization procedure, choosing the amount of GMS, the amount of phospholipid, the concentration of surfactant as the independent variables. The chosen dependent variables were entrapment efficiency, dosage loading, and particle size. The generated polynomial equations and response surface plots were used to relate the dependent and independent variables. The optimal nanoparticles were formulated with 100 mg GMS, 150 mg phospholipid, and 1% Tween80 and PEG 400 (1:1, w/v). A new formulation was prepared according to these levels. The observed responses were close to the predicted values of the optimized formulation. The particle size was 197.8 ± 4.9 nm. The polydispersity index of particle size was 0.239 ± 0.01 and the zeta potential was 32.7 ± 2.6 mV. The entrapment efficiency and dosage loading were about 68.39% and 2.49%, respectively. Fourier transform infrared spectroscopy (FT-IR) study indicated that the drug was entrapped in nanoparticles. The optimized formulation showed a sustained release followed the Peppas model. MTZ-SLNs showed significant prolonged decreasing intraocular pressure effect comparing with MTZ solution in vivo pharmacodynamics studies. The results of acute eye irritation study indicated that MTZ-SLNs and AZOPT both had no eye irritation. Furthermore, the MTZ-SLNs were suitable to be stored at low temperature (4 °C).

Successful treatment of recurrent epithelial ingrowth associated with interface fluid syndrome, flap necrosis, and epithelial defects following LASIK.

PURPOSE: to report the successful treatment of two patients who developed flap necrosis preceded by recurrent epithelial ingrowth and interface fluid syndrome after LASIK. METHODS: patient 1 was treated with epithelial debridement and flap suturing. Patient 2 was initially treated with epithelial debridement and flap suturing, but developed recurrent epithelial ingrowth in the right eye and 2 weeks later in the left eye. RESULTS: patient 1 developed diffuse interface fluid accumulation in the left eye after epithelial debridement and flap suturing and was treated with timolol meleate 0.5% solution and methazolamide. The interface fluid resolved and the cornea and flap became clear. Slit-lamp examination identified a small area of epithelial ingrowth recurrence, which has remained stable for 3 years. Patient 2 was successfully retreated with epithelial debridement followed by fibrin tissue adhesive application. Five months after debridement and fibrin tissue adhesive, no recurrence of epithelial ingrowth or interface fluid accumulation was noted. CONCLUSIONS: epithelial ingrowth and interface fluid syndrome may be associated with secondary flap necrosis following LASIK, which can be effectively treated with debridement and flap suturing or fibrin tissue adhesive application.

Treat ankylosing spondylitis with methazolamide.

BACKGROUND: Increased bone resorption and new bone information are two characteristics of ankylosing spondylitis (AS). Much evidence has shown that carbonic anhydrase inhibitors can restrain bone resorption. We had detected increased expression of carbonic anhydrase I (CA1) in synovium of patients with AS. This study aimed to evaluate the effectiveness and safety of methazolamide, an anti-carbonic anhydrase drug, for treating patients with AS. METHODS: Two patients, called as S and L, were diagnosed with active AS based on BASDAI and BASFI assessments, radiographic data and other clinical indices. They took methazolamide tablets at a dose of 25 mg twice every day. RESULTS: Patient S's BASDAI score fell from 5.4 to 4.4, while patient L's BASDAI fell from 2.4 to 2. Patient S's BASFI score change from 2.7 to 2.9, while patient L's BASFI score fell from 1.2 to 0.2. The ESR values of patient S were considerably reduced, while the ESR value of patient L remained unchanged and in the normal range. The calcium concentration of patient S decreased from 3.05 mmol/L to 2.39 mmol/L. The CT evidence indicates that the articular surfaces of the erosive sacroiliac joints became clearer and the area of the calcium deposits began decreased. No significant systemic side effects were observed in either patient. CONCLUSIONS: The above results indicate that methazolamide was effective for active AS. Methazolamide may improve AS symptoms by inhibiting carbonic anhydrase activity during the processes of bone reporption and new bone formation.

Preparation and evaluation of in situ gelling ophthalmic drug delivery system for methazolamide.

PURPOSE: In this study, a thermosensitive in situ gelling vehicle was prepared to increase the precorneal resident time and the bioavailability of methazolamide (MTA). METHOD: Poloxamer analogs were used as the gelling agents, and the in situ gel was obtained by using a cold method. The gelation temperature, rheological properties, in vitro release as well as in vivo evaluation (the elimination of MTA in aqueous humor and intraocular-lowering effect) of the optimized formulations were investigated. RESULTS: The optimum concentrations of poloxamer analogs for the in situ gel-forming delivery system were 21% (w/w) poloxamer 407 and 10% (w/w) poloxamer P188. This formulation was able to flow freely under nonphysiological conditions and underwent sol-gel transition in the cul-de-sac upon placement into the eye. In vitro release studies demonstrated a diffusion-controlled release of MTA from the poloxamer solutions over a period of 10 hours. In vivo evaluation indicated that the poloxamer solutions had a better ability to retain drug than MTA eyedrops did. CONCLUSION: These results suggested that in situ gelling ophthalmic drug delivery system may hold some promise in ocular MTA delivery.

Methazolamide calcium phosphate nanoparticles in an ocular delivery system.

A new system for the local delivery of methazolamide to the eye has been developed based on calcium phosphate (CaP) nanoparticles. The methazolamide loaded CaP nanoparticles were prepared through the formation of an inorganic core of CaP and further adsorption of the methazolamide. The maximum loading of methazolamide studied using UV-vis spectrophotometry was about 0.2% (w/w). The drug-loaded particles had a negative surface charge at about -30 mV while their mean particle diameter was estimated to be 256.4 nm. In vitro release studies demonstrated diffusion-controlled release of methazolamide from the CaP nanoparticles over a period of 4 h. In vivo studies indicated that the intraocular pressure (IOP)-lowering effect of the inorganic nanoparticle eye drops lasted for 18 h, which was significantly better than the effect of 1% brinzolamide eye drops (6 h). Physical stability studies indicated that the preparation was stable for 6 months at 40 degrees C. These findings suggested that methazolamide bound to CaP nanoparticles might be useful in the local treatment of glaucoma.

Comprehensive assessment of T cell receptor ß repertoire in Stevens-Johnson syndrome/toxic epidermal necrolysis patients using high-throughput sequencing.

Stevens-Johnson syndrome (SJS) /toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse drug reactions characterized by widespread epidermal necrosis. Recent studies have indicated that SJS/TEN is a specific immune reaction regulated by T cells. Certain drug serves as foreign antigens that are presented by major histocompatibility complex (MHC) and recognized by T cell receptors (TCRs), inducing adaptive immune responses. However, few studies have performed detailed characterization of TCR repertoire in SJS/TEN, and it remains unclear whether the particular types of TCRs expanded clonally are drug-specific, which would provide a potential underlying mechanism of SJS/TEN. In this study, using high-throughput sequencing, we comprehensively assessed the diversity, composition and molecular characteristics of the TCRß repertoires in 17 SJS/TEN patients associated with three different causative drugs including methazolamide (MZ), carbamazepine (CBZ) and allopurinol (ALP). Systematic analysis of the TCRß sequences revealed that SJS/TEN patients had more highly expanded clones and less TCR repertoire diversity, and the TCR repertoire diversity of these patients showed certain associations with the clinical severity of disease. Similar predominant clonotypes, shared-usage TRBV/TRBJ subtypes and combinations thereof were observed among different subjects with the same causative agent. Our observations provide enhanced understanding of the role of T lymphocytes in the pathogenesis of SJS/TEN and enumerate potential therapeutic targets.

Exploring optimized methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) crystalline cored micelles in anti-glaucoma pharmacotherapy.

Methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) polymeric micelles (PMs) open a promising avenue through which ocular drug delivery with superior efficacy and tolerability can be potentially obtained. Methazolamide (MTZ) is an anti-glaucoma drug exhibiting poor corneal penetration, making it an ideal candidate for new polymeric micellar systems. MTZ-PMs were prepared using the thin film hydration procedure and optimized using a Design of Experiment (DoE) approach. In vitro drug release, thermal analyses and FT-IR characterization were also evaluated. MTT assay and histopathological assessment were carried out to verify ocular tolerability as well as Draize irritancy test. In vivo studies were conducted on rabbits to evaluate anti-glaucoma activity in a glucocorticoid-induced glaucoma model. The results showed successful entrapment of MTZ inside PMs matrix as reflected by the complete vanishing of drug melting peak in DSC thermogram and the possible formation of hydrogen bonding between MTZ and mPEG-PCL copolymer in FT-IR spectrum. The selected formula exhibited a particle size of 60 nm, entrapment efficiency of 93% and discrete spherical particles. Moreover, sustained release of MTZ, cellular and tissue biocompatibility and marked anti-glaucoma efficacy, as compared to MTZ solution, were realized. The combined results show that PMs could potentiate the therapeutic outcome of nanotechnology ocular drug delivery.

Therapeutic Efficacy of Methazolamide Against Intermittent Hypoxia-Induced Excessive Erythrocytosis in Rats.

Zhang, Zhiqing, Zhonghai Xiao, Bingnan Deng, Xiaohua Liu, Wei Liu, Hongjing Nie, Xi Li, Zhaoli Chen, Danfeng Yang, and Ruifeng Duan. Therapeutic efficacy of methazolamide against intermittent hypoxia-induced excessive erythrocytosis in rats. High Alt Med Biol 19:69-80, 2018.-This study aimed to determine whether methazolamide is effective for the treatment of chronic mountain sickness. Forty-eight male Wistar rats were randomly divided into eight groups: normoxia control, hypoxia control, hypoxia + acetazolamide (30 mg·kg-1·d-1), and five hypoxia + methazolamide groups (5, 10, 30, 90, and 120 mg·kg-1·d-1). Excessive erythrocytosis was induced through 4 weeks of hypobaric hypoxia (8 hours O2 10%/16 hours O2 21%). Rats were then treated for 4 weeks, and their body weight was measured. Hematological, hemorheological, and biochemical parameters were analyzed. Renal hypoxia-inducible factor-1alpha (HIF-1α) and vascular endothelial growth factor (VEGF) levels were detected by immunohistochemistry. Proteomic analysis of plasma was conducted to determine the most differentially expressed proteins. Methazolamide with doses lower than 30 mg·kg-1·d-1 had no significant effects on body weight compared with the hypoxia control group (p > 0.05). Methazolamide dose-dependently reduced the hemoglobin concentration, hematocrit (Hct), and blood viscosity. Hct/blood viscosity, an oxygen delivery index, dose-dependently increased after methazolamide treatment. A methazolamide dose of 10 mg·kg-1·d-1 showed similar efficacy to an acetazolamide dose of 30 mg·kg-1·d-1 for all the above parameters. Plasma levels of low-density lipoprotein cholesterol, total cholesterol, creatinine, and hemoglobin increased substantially after long-term hypoxia, but decreased after methazolamide treatment. HIF-1α and VEGF both increased substantially after long-term hypoxia and decreased in the kidney after methazolamide treatment. The most differentially expressed protein was haptoglobin, an endogenous protective factor, which was depleted in rats with excessive erythrocytosis and increased substantially after methazolamide treatment. In summary, methazolamide exhibits dose-dependent efficacy for the treatment of excessive erythrocytosis induced by long-term hypoxia. It also has beneficial effects on oxygen transport and lipid metabolism, which are encouraging with regard to the development of methazolamide-based chronic mountain sickness therapies.

Methazolamide improves neurological behavior by inhibition of neuron apoptosis in subarachnoid hemorrhage mice.

Subarachnoid hemorrhage (SAH) results in significant nerve dysfunction, such as hemiplegia, mood disorders, cognitive and memory impairment. Currently, no clear measures can reduce brain nerve damage. The study of brain nerve protection after SAH is of great significance. We aim to evaluate the protective effects and the possible mechanism of methazolamide in C57BL/6J SAH animal model in vivo and in blood-induced primary cortical neuron (PCNs) cellular model of SAH in vitro. We demonstrate that methazolamide accelerates the recovery of neurological damage, effectively relieves cerebral edema, and improves cognitive function in SAH mice as well as offers neuroprotection in blood- or hemoglobin-treated PCNs and partially restores normal neuronal morphology. In addition, western blot analyses show obviously decreased expression of active caspase-3 in methazolamide-treated SAH mice comparing with vehicle-treated SAH animals. Furthermore, methazolamide effectively inhibits ROS production in PCNs induced by blood exposure or hemoglobin insult. However, methazolamide has no protective effects in morality, fluctuation of cerebral blood flow, SAH grade, and cerebral vasospasm of SAH mice. Given methazolamide, a potent carbonic anhydrase inhibitor, can penetrate the blood-brain barrier and has been used in clinic in the treatment of ocular conditions, it provides potential as a novel therapy for SAH.

Methazolamide Plus Aminophylline Abrogates Hypoxia-Mediated Endurance Exercise Impairment.

In hypoxia, endurance exercise performance is diminished; pharmacotherapy may abrogate this performance deficit. Based on positive outcomes in preclinical trials, we hypothesized that oral administration of methazolamide, a carbonic anhydrase inhibitor, aminophylline, a nonselective adenosine receptor antagonist and phosphodiesterase inhibitor, and/or methazolamide combined with aminophylline would attenuate hypoxia-mediated decrements in endurance exercise performance in humans. Fifteen healthy males (26 ± 5 years, body-mass index: 24.9 ± 1.6 kg/m(2); mean ± SD) were randomly assigned to one of four treatments: placebo (n = 9), methazolamide (250 mg; n = 10), aminophylline (400 mg; n = 9), or methazolamide (250 mg) with aminophylline (400 mg; n = 8). On two separate occasions, the first in normoxia (FIO2 = 0.21) and the second in hypoxia (FIO2 = 0.15), participants sat for 4.5 hours before completing a standardized exercise bout (30 minutes, stationary cycling, 100 W), followed by a 12.5-km time trial. The magnitude of time trial performance decrement in hypoxia versus normoxia did not differ between placebo (+3.0 ± 2.7 minutes), methazolamide (+1.4 ± 1.7 minutes), and aminophylline (+1.8 ± 1.2 minutes), all with p > 0.09; however, the performance decrement in hypoxia versus normoxia with methazolamide combined with aminophylline was less than placebo (+0.6 ± 1.5 minutes; p = 0.01). This improvement may have been partially mediated by increased SpO2 in hypoxia with methazolamide combined with aminophylline compared with placebo (73% ± 3% vs. 79% ± 6%; p < 0.02). In conclusion, coadministration of methazolamide and aminophylline may promote endurance exercise performance during a sojourn at high altitude.

Acetazolamide-like carbonic anhydrase inhibitors with topical ocular hypotensive activity.

New carbonic anhydrase (EC 4.2.1.1) inhibitors were synthesized as potential drugs for the topical treatment of glaucoma. They were obtained by substituting the acetyl group of acetazolamide and methazolamide with bicarboxylic acids of different chain length (C4-C6). The terminal carboxyl was either kept free or esterified with alcohols of different size (C1-C12). A gamma-aminovaleric derivative was also prepared. All compounds proved active as carbonic anhydrase inhibitors in vitro, with an average IC50 of about 0.5 microM. Some proved also to be topically active in vivo in lowering the artificially elevated intraocular pressure in rabbits. The most active compound, carrying a succinic acid side chain, is the most soluble in aqueous buffers. Its duration of action is about 8 h and it is under evaluation as a topical antiglaucoma drug. It is hypothesized that the duration of action could be longer in compounds having both the same high water solubility and partition coefficient.

The effects of carbonic anhydrase inhibitors on aqueous humor chemistry and dynamics.

The effects of topical application of the carbonic anhydrase inhibitor trifluormethazolamide (TFM) on intraocular pressure (IOP), ascorbate and CO2 concentrations in aqueous humor, and aqueous humor flow were studied in rabbits. These effects were compared with those produced by systemic treatment with methazolamide. The decrease in IOP observed after TFM was accompanied by changes in the composition of the aqueous humor. Posterior aqueous ascorbate concentration showed a marked increase (up to 1.7-fold), whereas the anterior aqueous ascorbate did not change significantly. Similar changes were found in rabbits after systemic treatment with methazolamide. A small but statistically significant decrease in the CO2 content of both posterior and anterior aqueous was observed after topical TFM application. Methazolamide yielded a more profound lowering in the CO2 content of the aqueous humor, a reflection of the significant decrease in plasma CO2 content. For topical TFM or systemic methazolamide doses yielding complete inhibition of carbonic anhydrase in the eye, a 55-59% reduction of aqueous flow was calculated from the ascorbate data using the Kinsey and Palm equation. However, a 31-42% reduction in aqueous flow was obtained from the same data using an equation based only on posterior chamber data. The reasons for using only posterior aqueous ascorbate data for calculating the changes in aqueous humor flow are discussed.

Methazolamide 1% in cyclodextrin solution lowers IOP in human ocular hypertension.

PURPOSE: To formulate aqueous eye drops containing methazolamide 1% in cyclodextrin solution and to evaluate their effect on intraocular pressure (IOP) in a double-blind randomized trial in humans. Methazolamide, a carbonic anhydrase inhibitor (CAI), has been used in oral doses in the treatment of glaucoma but hitherto has not been successfully formulated in eye drops. In this study the effects of methazolamide are compared with those of dorzolamide (Trusopt). METHODS: Methazolamide 1% was formulated in a 2-hydroxypropyl-beta-cyclodextrin with hydroxypropyl methylcellulose in aqueous solution. Eight persons with ocular hypertension were treated with the methazolamide-cyclodextrin eye drops and eight persons with dorzolamide (Trusopt), both groups at dosages of three times a day for 1 week. IOP was measured before treatment was begun and on days 1, 3, and 8 at 9 AM (peak) and 3 PM (trough). RESULTS: After 1 week of treatment, the peak IOP in the methazolamide group had decreased from 24.4 +/- 2.1 mm Hg (mean +/- SD) to 21.0 +/- 2.0 mm Hg, which is a 14% pressure decrease (P: = 0.006). In the dorzolamide group, the peak IOP decreased from 23.3 +/- 2.1 mm Hg to 17.2 +/- 3.1 mm Hg, which is a 26% pressure decrease (P: < 0.001). On average, the IOP declined 3.4 +/- 1.8 mm Hg after methazolamide administration and 6.1 +/- 3.6 mm Hg after dorzolamide. CONCLUSIONS: Through cyclodextrin complexation, it is possible to produce topically active methazolamide eye drops that lower IOP. This is the first double-blind clinical trial that demonstrates the efficacy of the classic CAIs in eye drop formulation.

Treatment of essential tremor with methazolamide.

We treated 28 patients (16 women and 12 men) who had essential tremor with methazolamide. Their median age was 69 years (range, 34 to 89 years), and the median duration of tremor was 16 years (range, less than 1 to 69 years). Fifteen cases were familial and 13 were sporadic. Improvement in 10 patients who continued taking the drug ranged from moderate to complete relief. In addition, four patients had marked improvement and two had moderate improvement but discontinued use of the drug because of side effects. Five patients with a mild response and seven with no response also discontinued methazolamide therapy. The maximal mean daily dose was 203 mg for all patients and 129 mg (maintenance dose) for the patients who continued taking the drug. Side effects consisted primarily of somnolence, nausea, epigastric discomfort, anorexia, paresthesias, and numbness. No aplastic anemia was noted in any of the patients. The median duration of follow-up was 6 months (range, 10 weeks to 29 months). The therapeutic effect seemed unrelated to a family history of tremor, the effect of alcohol, or the responsiveness to propranolol or primidone. Methazolamide may be an effective drug in the treatment of some patients with essential tremor, particularly those with head and voice tremor.

A repeated dose-response study of methazolamide in glaucoma.

Twenty-two patients with open-angle glaucoma were given weekly courses of methazolamide at different dosages. Mean intraocular pressure reductions of 3.3, 4.3, and 5.6 mm Hg were achieved at dosages of 25 mg, 50 mg, and 100 mg of methazolamide every eight hours, respectively. Maximal intraocular pressure lowering was still present nine to ten hours after administration. The mean reduction in outflow pressure for all eyes receiving a daily dosage of 300 mg was only 31%, but this included eyes (17% of the total) that demonstrated less than 13% reduction in outflow pressure, despite similar methazolamide serum levels. Eight patients subsequently received acetazolamide, 250 mg four times a day for a week. The effect of this dosage of acetazolamide on pressure was between the effects of 50 and 100 mg of methazolamide three times daily.

Topical acetazolamide and methazolamide delivered by contact lenses.

Topical acetazolamide has been previously found to be ineffective in lowering intraocular pressure (IOP). Using high-water-content soft contact lenses (Sauflon PW) soaked in acetazolamide, we observed a statistically significant ipsilateral decrease in IOP of 6.3 +/- 0.4 mm Hg in the treated eyes of albino rabbits. The duration of the effect was up to 7 1/2 hours. Methazolamide-soaked contact lenses produced a maximum unilateral reduction of similar magnitude but shorter duration. Both serum and aqueous humor analyses for pH, carbon dioxide pressure, bicarbonate, and base excess indicate that acetazolamide delivered by soft contact lenses is able to penetrate the cornea in sufficient concentration to lower IOP by a local mechanism in rabbits without significant systemic absorption.

Intraocular pressure effects of carbonic anhydrase inhibitors in primary open-angle glaucoma.

We tested the effect on intraocular pressure of three commonly used oral carbonic anhydrase inhibitor preparations in a controlled, randomized, comparative study on patients with primary open-angle glaucoma. Preparations tested included acetazolamide tablets, acetazolamide Sequels, and methazolamide tablets. The effect of the three carbonic anhydrase inhibitors was assessed by using a statistical modeling approach as well as by evaluating the average maximum reduction in intraocular pressure for each preparation. Dosage and time effects were also determined. As expected, each drug preparation was more effective in reducing intraocular pressure when administered to a patient who had already been treated with the carbonic anhydrase inhibitor preparation. The amount of intraocular pressure lowering was directly related to dose for both acetazolamide preparations. Of particular interest was the finding that maximal rapid reduction of intraocular pressure was obtained with a 500-mg dosage of acetazolamide tablets.

The effect of topically administered carbonic anhydrase inhibitors on aqueous humor dynamics in rabbits.

Repeated topical administration of 2.5% trifluormethazolamide, a halogenated derivative of methazolamide, resulted in a unilateral decrease in intraocular pressure in rabbits. Mean (+/- S.E.M.) baseline intraocular pressure (19.8 +/- 2.1 mm Hg) was significantly (P less than .05) decreased 30 minutes (16.1 +/- 2.2 mm Hg) and 60 minutes (15.8 +/- 2.7 mm Hg) after drug administration. Trifluormethazolamide did not alter outflow facility. Aqueous humor flow calculated from the tonographic data was reduced 44% and flow measured by fluorophotometry was reduced 29%. Topical delivery of trifluormethazolamide decreased the level of carbon dioxide in the aqueous humor in the treated eye in a manner similar to that observed after systemic administration of carbonic anhydrase inhibitors. Topical administration of 10% acetazolamide did not decrease intraocular pressure. However, topical administration of either trifluormethazolamide or acetazolamide before oral administration of water resulted in a blunting of the water-induced ocular hypertensive response.

Low-dose methazolamide and intraocular pressure.

Sixteen patients with increased intraocular pressure (over 20 mm Hg) received 25 and 50 mg of oral methazolamide, twice daily, during consecutive weeks and then 500 mg (Sequels) of acetazolamide. The two methazolamide regimens produced significant decreases in intraocular pressure. Acetazolamide treatment resulted in a greater decrease in intraocular pressure but more systemic acidosis and side effects.