Disease relevance of methazolamide

• Aplastic anemia and agranulocytosis in patients using methazolamide for glaucoma [1].
• Methazolamide in acute mountain sickness [2].
• Double-blind controlled study of methazolamide in the treatment of essential tremor [3].
• Neutropenia with clozapine and methazolamide [4].
• Methazolamide 1% in cyclodextrin solution lowers IOP in human ocular hypertension [5].

Psychiatry related information on methazolamide

• The anticonvulsant action of phenytoin, phenobarbital and of 3 carbonic anhydrase inhibitors: methazolamide, acetazolamide, ethoxzolamide, was assessed in rats subjected to maximal electroshock [6].

High impact information on methazolamide

• These pH effects were not inhibited by the presence of luminal bumetanide (1 mmol/L), furosemide (1 mmol/L), hydroflumethiazide (1 mmol/L), or 4,4'-diisothiocyanostilbene-2,2'-disulfonate (1 mmol/L), or by the carbonic anhydrase inhibitor methazolamide (1 mmol/L) [7].
• A hydrogen bond network involving solvent molecules and active site residues His200 and His67 amongst others in the native enzyme, is disrupted upon binding of methazolamide but not in the other two sulfonamides [8].
• We studied the effect of the carbonic anhydrase inhibitor methazolamide in 25 patients with essential tremor (ET) in a double-blind, placebo-controlled trial [3].
• Some clinically used compounds, such as acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, topiramate, sulpiride, and indisulam, or the orphan drug benzolamide, showed effective hCA VI inhibitory activity, with inhibition constants of 0.8-79 nM [9].
• The observation that even high-dose methazolamide, causing full inhibition of carbonic anhydrase in all body tissues, did not reduce the hypoxic ventilatory response is reminiscent of previous findings by others showing no change in magnitude of the hypoxic response of the in vitro carotid body by this agent [10].

Chemical compound and disease context of methazolamide

• Several case reports of aplastic anemia with use of acetazolamide, and two cases with use of methazolamide, have appeared in the literature [1].
• Focal tissue acidosis was produced by blockade of carbonic anhydrase with either focal acetazolamide (AZ) or methazolamide (MZ) microinjection [11].
• Three subjects who had an initial improvement in their macular edema as demonstrated on fluorescein angiography received a continued course of methazolamide to assess its effect on macular edema [12].

Biological context of methazolamide

• 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 [5].
• The other is an HCO3- -dependent, methazolamide-sensitive system, and is probably an Na+/H+ antiport [13].
• In glands perfused with HCO3- and ise -, the addition of methazolamide, an inhibitor of carbonic anhydrase, caused a further 60% drop in secretory rate, but the saliva remained rich in HCO3-. Replacement of perfusate HCO3- with Cl- or ise - had no effect on salivary secretion or composition [13].
• The carbonic anhydrase inhibitor methazolamide was used to test the hypothesis that carbonic anhydrase activity plays a role in the early morphogenesis of the chick eye [14].
• As a group, visual acuity statistically improved with methazolamide [15].

Anatomical context of methazolamide

• Methazolamide yielded a more profound lowering in the CO2 content of the aqueous humor, a reflection of the significant decrease in plasma CO2 content [16].
• Due to their salt-like character, the new type of inhibitors reported here, unlike the classical, clinically used compounds (such as acetazolamide, methazolamide, and ethoxzolamide), are unable to penetrate through biological membranes, as shown by ex vivo and in vivo perfusion experiments in rats [17].
• Methazolamide was administered topically to eyes of 4-7-day-old chick embryos in shell-free culture [14].
• 6. The changes in slope and intercept induced by methazolamide are discussed in relation to effects on neurones containing carbonic anhydrase, which may include central chemoreceptors [18].
• 2. In the same animals the effect on the ventilatory response to CO2 of subsequent inhibition of central nervous system (CNS) carbonic anhydrase was studied by infusing methazolamide (20 mg kg-1), an inhibitor which rapidly penetrates into brain tissue [18].

Associations of methazolamide with other chemical compounds

• Rat duodena were perfused with solutions of different pH and PCO2 with or without a cell-permeant CA inhibitor methazolamide (MTZ) or impermeant CA inhibitors [19].
• Additionally, TRH and MK-771 restored the anticonvulsant actions of methazolamide in mice pretreated with reserpine or picolinic acid [20].
• Calcium metabolism and its response to citrate were examined in 51 patients with glaucoma receiving carbonic anhydrase inhibitors (acetazolamide or methazolamide) [21].
• Anion transport inhibitor DIDS, anion channel inhibitor 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), carbonic anhydrase inhibitor methazolamide, and nonselective cyclooxygenase inhibitor indomethacin were used to inhibit separate components of HCO(3)(-) secretory pathway [22].
• The reactivities toward conjugation at pH 7.5 within two series of 5-substituted 1,3,4-thiadiazole- and 1,3,4-thiadiazoline-2-sulfonamides (methazolamide derivatives) conformed to the Brønsted relationship, the rate of conjugation increasing as sulfonamide pK, decreased [23].

Gene context of methazolamide

• An interesting behavior was evidenced for some of the ortho-substituted arylsulfonylcarbamato-sulfonamides, which showed higher affinities for the isozyme hCA I, as compared to hCA II and bCA IV (generally hCA I is 10-1000 less sensitive to "normal" sulfonamide inhibitors, such as acetazolamide, methazolamide or dorzolamide, as compared to hCA II) [24].
• Inhibition of CA (methazolamide, 25 mg/kg) led in all groups to equivalent increments of urine pH, urine flow, and HCO3-, Na+, and K+ excretion [25].
• Some of these derivatives showed good inhibitory potency against two human CA isozymes involved in important physiological processes, CA I, and CA II, of the same order of magnitude as the clinically used drugs acetazolamide and methazolamide [26].
• The inhibition of the newly discovered cytosolic carbonic anhydrase isozyme XIII (CA XIII) has been investigated with a series of aromatic and heterocyclic sulfonamides, including some of the clinically used derivatives, such as acetazolamide, methazolamide, dichlorophenamide, dorzolamide, and valdecoxib [27].
• 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 [28].

Analytical, diagnostic and therapeutic context of methazolamide

• METHODS: Seventeen subjects with retinitis pigmentosa and chronic macular edema participated in a prospective, placebo-controlled, double-masked, crossover design study in which either methazolamide or a placebo was taken for 3 weeks [15].
• Temporal patterns of methazolamide concentrations in plasma and red blood cells were obtained following single- and multiple-dose oral administration of the drug [29].
• Methazolamide-soaked contact lenses produced a maximum unilateral reduction of similar magnitude but shorter duration [30].
• In the present study, an analytical method using high performance liquid chromatography was validated for determination of methazolamide concentrations in several biological fluids [31].
• Repeated topical administration of 2.5% trifluormethazolamide, a halogenated derivative of methazolamide, resulted in a unilateral decrease in intraocular pressure in rabbits [32].

References