SEARCH · PubMed Health

Results for “METHAZOLAMIDE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed1979

Aplastic anemia and agranulocytosis in patients using methazolamide for glaucoma.

Carbonic anhydrase inhibitors used in the treatment of glaucoma, seizure disorders, and hypertension are rarely associated with blood dyscrasias. Several case reports of aplastic anemia with use of acetazolamide, and two cases with use of methazolamide, have appeared in the literature. This article describes two cases of aplastic anemia, at least one of which was almost certainly induced by the use of methazolamide, and one case of agranulocytosis related to the use of methazolamide.

Aged↗

PubMedDate not supplied

Methazolamide-induced delirium.

A 74-year-old man became delirious 2 days after beginning oral therapy with methazolamide. The delirium was manifested by intermittent psychosis, incontinence of bowel and bladder, lethargy, and disorientation. These symptoms continued for 25 days despite many changes in his drug regimen, and complete laboratory, urologic, and neurologic work-ups. The symptoms resolved completely within 1 week of discontinuing methazolamide. This is the first case reported of delirium associated with methazolamide not accompanied by a metabolic imbalance.

Aged↗

PubMed1981

Time course and disposition of methazolamide in human plasma and red blood cells.

Methazolamide was determined in plasma, whole blood, and urine by a GLC-mass spectrometric method. Temporal patterns of methazolamide concentrations in plasma and red blood cells were obtained following single- and multiple-dose oral administration of the drug. The nonlinearity in the binding of the drug to the red blood cell carbonic anhydrase was evident from a comparison of plasma and red blood cells concentrations. The drug was cleared slowly from the red blood cells. The binding constants to the two isoenzymes of carbonic anhydrase were determined from the plasma and red blood cell concentrations and were in agreement with those determined by previous measurements. The half-life of elimination was 7.5 hr. The urinary recovery of unchanged drug was approximately 25% of the administered dose.

Carbonic Anhydrases↗

PubMed1990

Glutathione conjugation of methazolamide and subsequent reactions in the ciliary body in vitro.

Conjugation reaction of methazolamide with glutathione and its subsequent reactions were studied in vitro. Glutathione, cysteinylglycine, and cysteine conjugates of methazolamide were chemically synthesized. All of the three compounds showed absorbance below 330 nm, with maximal absorbance at approximately 300 nm. At the wavelengths below 220 nm, absorbance was proportional to the number of the amino acids each compound had. Amino acid analysis of the glutathione conjugate showed that the conjugation reaction involved the cysteine residue of glutathione. In order to identify the chemical structure of the reaction product, cysteine conjugate was subjected to infrared, proton nuclear magnetic resonance, and mass spectral analyses. These studies indicated that the cysteine conjugate was S-(5-acetylimino-4-methyl-delta 2-1,3,4-thiadiazolinyl)cysteine. The reaction with glutathione was not catalyzed by glutathione S-transferases, but proceeded in the absence of the enzyme. The glutathione conjugate was degraded by bovine ciliary body homogenate to the cysteinylglycine conjugate and then to the cysteine conjugate.

Animals↗

PubMed1979

The intraocular pressure responses of low-dose bupranolol (Ophtorenin) and methazolamide (Neptazane) in glaucomatous eyes. A controlled clinical study.

In a single-dose, double-blind study, the minimum effective doses of bupranolol and methazolamide were established. The beta-blocker bupranolol (Ophtorenin, Dr. Winzer, Konstanz) in an oily solution reduced IOP significantly in a concentration of 0.05%. The carboanhydrase inhibitor Methazolamide (Neptazane) did not change IOP in a peroral dose of 50 mg, while 100 mg p.o. gave a significant IOP decrease. Both drugs exhibited an additive effect in this low regimen. It is concluded that the combined application of both drugs will postpone or avoid side effects and prolong the time and the field of clinical usefulness. It appears possible that both have a different mechanism of action.

Bupranolol↗

PubMed1976

Urinary calculus during methazolamide therapy.

A 68-year-old white man with Paget's disease and open-angle glaucoma was treated with methazolamide, 50 to 100 mg three times daily. Ten months after the medication was initiated he developed ureteral colic and a calcium oxalate stone was surgically removed. Three months after the drug was reinstituted the patient passed three calcium phosphate stones. This suggested a casual relationship between methazolamide and stone formation, although renal calculi also complicate Paget's disease and acetazolamide had been administered briefly.

Acetazolamide↗

PubMed1977

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.

Acetazolamide↗

PubMed1978

Nonfatal methazolamide-induced aplastic anemia.

An 83-year-old man developed nonfatal aplastic anemia after taking methazolamide for three months. We made a diagnosis of methazolamide-induced aplastic anemia, discontinued all medication, gave the patient platelet and red blood cell transfusions, and treated him with oxymetholone. Approximately four months after initiation of treatment, the patient felt well, and he is currently receiving packed red blood cell transfusions every three weeks.

Acetazolamide↗

PubMed1977

The anticonvulsant action of methazolamide in mice: antagonism by various inhibitors of dopamine beta-hydroxylase.

The dopamine beta-hydroxylase inhibitors, FLA-63 and picolinic acid, antagonized the anticonvulsant action of methazolamine in mice; disulfiram and pyrimidinethiol were inactive. FLA-63 and picolinic acid, but not disulfiram or pyrimidinethiol prevented pheniprazine restoration of the anticonvulsant action of methazolamide in reserpinized mice. The present findings clearly demonstrate that differences exist among inhibitors of dopamine beta-hydroxylase regarding their ability to antagonize the anticonvulsant action of methazolamide under various test conditions.

Animals↗

PubMed1995

Metal complexes of the carbonic anhydrase inhibitor methazolamide (Hmacm). Crystal structure of the Zn(macm)2(NH3)2. Anticonvulsant properties of the Cu(macm)2(NH3)3(H2O).

Complexes of Co(II), Cu(II), and Zn(II) with deprotonated methazolamide and ammonia are synthesized and characterized. The complex Zn(macm)2(NH3)2 crystallizes in the monoclinic C2/c space group with a = 13.468(1), b = 6.759(1), c = 23.014(2) A, beta = 90.27(1), and Z = 4. The structure was refined to R = 0.049 (Rw = 0.053). The Zn(II) ion is coordinated to two deprotonated sulfonamido nitrogen atoms of the macm- ligand and two nitrogen atoms of the ammonia ligands in a distorted tetrahedron. The Zn(macm)2(NH3)2 complex is shown to be a simple model for the methazolamide inhibition of CA. EHMO calculations applied to fractional coordinates of the Zn(macm)2(NH3)2 complex indicate that the atomic orbitals of the Zn do not contribute to HOMO and LUMO of the complex. The characteristics of the Cu(macm)2(NH3)3(H2O) as an anticonvulsant agent are tested.

Animals↗

PubMed1999

In vitro characterization of the erythrocyte distribution of methazolamide: a model of erythrocyte transport and binding kinetics.

The rate and extent of binding of methazolamide to human erythrocytes was studied in vitro. All experiments were carried out at physiological temperature (37 C) and pH (7.4). Methazolamide (MTZ) buffer concentrations were analyzed by HPLC. Distributional equilibrium between buffer and washed red blood cells was achieved after 1 hr. Results of equilibrium studies were consistent with two classes of binding sites for MTZ within the erythrocyte: a low affinity, high capacity site (CA-I) and a high affinity, low capacity site (CA-II). A two-binding site model was fitted to experimental data generating estimates for binding parameters Ka1 (0.0017 +/- 0.00022 microM-1) nM1 (636 +/- 5.23 microM), Ka2(0.46 +/- 0.0083 microM-1), and nM2(80.9 +/- 0.389 microM). Based upon these findings, kinetic studies were performed in order to characterize the rate of drug distribution. The rate of erythrocyte uptake of MTZ was mathematically modeled using a series of differential equations describing drug diffusion across the red blood cell membrane and subsequent complexation with intracellular binding sites. The model assumed that penetration of MTZ into the red blood cells was passive but drug binding to the carbonic anhydrase isozymes was not instantaneous. Using a novel curve fitting technique, parameter estimates of RBC membrane permeability (0.0102 +/- 0.000618 cm/min), and binding rate constants k-1(0.254 +/- 0.0213 min-1), k1 (0.0022 +/- 0.00020 ml/microgram-min), k-2(1.59 +/- 0.0358 min-1), and k2(3.1 +/- 0.035 ml/microgram-min) were obtained. The model characterized the observed biphasic decline of MTZ buffer concentrations over time and may help explain the prolonged residence of MTZ in vivo.

Binding Sites↗

PubMed2002

Carbachol-induced fluid movement through methazolamide-sensitive bicarbonate production in rat parotid intralobular ducts: quantitative analysis of fluorescence images using fluorescent dye sulforhodamine under a confocal laser scanning microscope.

Fluid secretion is observed at the openings of ducts in the exocrine gland. It remains unclear whether the ducts are involved in fluid secretion in the salivary glands. In the present study, we investigated the exclusion of fluorescent dye from the duct lumen by carbachol (CCh) in isolated parotid intralobular duct segments to clarify the ability of the ducts for the fluid secretion. When the membrane-impermeable fluorescent dye, sulforhodamine, was added to the superfused extracellular solution, quantitative fluorescence images of the duct lumen were obtained under the optical sectioning at the level of the duct lumen using a confocal laser scanning microscope. CCh decreased the fluorescent intensity in the duct lumen during the superfusion of the fluorescent dye, and CCh flushed out small viscous substances stained with the fluorescent dye from isolated duct lumen, suggesting that CCh might induce fluid secretion in the duct, leading to the clearance of the dye and small stained clumps from the duct lumen. CCh-induced clearance of the fluorescent dye was divided into two phases by the sensitivity to external Ca2+ and methazolamide, an inhibitor for carbonic anhydrase. The initial phase was insensitive to these, and the subsequent late phase was sensitive to these. A major portion in the late phase was inhibited by removal of bicarbonate in the superfusion solution and DPC, but not low concentration of external Cl-, bumetanide or DIDS, suggesting that methazolamide-sensitive production of HCO3-, but not the Cl- uptake mechanism, might contribute to the CCh-induced clearance of the dye from the duct lumen. These results represent the first measurements of fluid movement in isolated duct segments, and suggest that carbachol might evoke fluid secretion possibly through Ca2+-activated, DPC-sensitive anion channels with HCO3- secretion in the rat parotid intralobular ducts.

Animals↗

PubMed2003

Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with the perfluorobenzoyl analogue of methazolamide. Implications for the drug design of fluorinated inhibitors.

The X-ray crystal structure for the adduct of human carbonic anhydrase (hCA) II with 4-methyl-5-perfluorophenylcarboximido-delta2-1,3,4-thiadiazoline-2-sulfonamide (PFMZ), a topically acting antiglaucoma sulfonamide, has been resolved at a resolution of 1.8 A. This compound is almost 10 times more effective as a hCA II inhibitor (KI of 1.5 nM) compared to the lead molecule, methazolamide, a clinically used drug (KI of 14 nM). Its binding to the enzyme active site is similar to that of other sulfonamide inhibitors, considering the interactions of the sulfonamide zinc anchoring group and thiadiazoline ring contacts, but differs considerably when the perfluorobenzoylimino fragment of the molecule is analyzed. Indeed, several unprecedented strong hydrogen bonds involving the imino nitrogen, carbonyl oxygen, a fluorine atom in the ortho position of the inhibitor, and two water molecules, as well as Gln 92 of the enzyme active site were seen. A stacking interaction of the perfluorophenyl ring of the inhibitor and the aromatic ring of Phe 131 was also observed for the first time in a CA-sulfonamide adduct. All these findings prove that more potent CA inhibitors incorporating perfluoroaryl/alkyl tails may be designed, with potentially improved antiglaucoma properties, in view of the new types of interactions seen here between the enzyme and the perfluorobenzoylated analogue of methazolamide.

Binding Sites↗

PubMed1983

Methazolamide and acetazolamide in acute mountain sickness.

Methazolamide (150 mg/d) was as effective as acetazolamide (500 mg/d) in preventing the symptoms of acute mountain sickness in 20 subjects ascending to 4985 m. PaO2 and oxygen saturation levels were similar on the two drugs but the fall in PaCO2 was greater on acetazolamide. Paraesthesiae, a side-effect of carbonic anhydrase inhibitors, tended to be less at high altitude on methazolamide and was significantly less when taking 100 mg/d at low altitude. It is likely that paraesthesiae is similar on the two drugs when given in doses that affect blood gases equally.

Acetazolamide↗

PubMed1985

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.

Acetazolamide↗

PubMed1993

Methazolamide-induced skin eruptions.

To our knowledge, this is the first histopathologic report of skin eruptions due to oral methazolamide. From the four cases studied, we conclude that there are at least two histopathologic types: one is characterized by perivascular lymphocytic infiltrate with a vacuolar alteration at the dermoepidermal junction, the other by perivascular eosinophils, lymphocytes, and scattered mast cells. There also seem to be at least two patterns of skin eruptions: one maculopapular and the other urticarial. The type of skin eruption and the histopathologic type appear to be related.

Administration, Oral↗

PubMed1998

Blood disposition and urinary excretion kinetics of methazolamide following oral administration to human subjects.

The pharmacokinetic disposition of methazolamide (MTZ) was studied in five healthy volunteers following administration of a single oral dose. Drug concentrations in blood, plasma, and urine were measured by HPLC. Over the range of plasma concentrations observed in vivo, MTZ free fraction (measured by ultrafiltration) was 0.28. Being a carbonic anhydrase inhibitor, MTZ would be expected to distribute into, and be sequestered by, red blood cells. For this reason, MTZ disposition was characterized utilizing blood concentrations as the reference. Using a two-compartment model, a series of differential equations were simultaneously fitted to blood concentrations and urinary excretion data generating estimates for k10 (0.035 +/- 0.019 h(-1)), k12 (0.200 +/- 0.036 h(-1)), k21 (0.077 +/- 0.046 h(-1)), k(a) (0.304 +/- 0.064 h(-1)), Vc (1.1 +/- 0.18 L) and f(r) (fraction excreted renally, 0.61 +/- 0.14). Total blood clearance was 0.037 +/- 0.020 L h(-1). The model estimate of elimination half-life (126 +/- 61 h) was consistent with drug binding to a high affinity carbonic anhydrase isozyme in the erythocyte. Estimates of MTZ renal clearance and renal excretion ratio were 0.021 +/- 0.010 L h(-1) and 0.16 +/- 0.06, respectively. Overall, the prolonged elimination of MTZ from the blood is the result of extensive erythrocyte distribution and tubular reabsorption by the kidney.

Administration, Oral↗

PubMed2001

Cysteine conjugate of methazolamide is metabolized by beta-lyase.

Bovine kidney and liver homogenates degraded a cysteine conjugate of methazolamide, S-(5-acetylimino-4-methyl-Delta2-1,3,4-thiadiazolin-2-yl)cysteine. We isolated the degradation product following incubation with kidney homogenate by high-performance liquid chromatography on reversed-phase columns. The chemical structure was confirmed by proton and carbon-13 nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR, respectively), and elemental analysis by high-resolution mass spectrometry to be N-(3-methyl-5-mercapto-Delta4-1,3,4-thiadiazol-2-yl)acetamide, a thiol compound. The reaction is thought to be catalyzed by a pyridoxal-dependent enzyme(s) as indicated by an inhibition study using aminooxyacetic acid. Possible involvement of the thiol compound in the development of an adverse effect is discussed.

Animals↗