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Results for “METHAZOLAMIDE”

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PubMed1984

Effect of bicarbonate, pH, methazolamide and stilbenes on the intracellular potentials of cultured bovine corneal endothelial cells.

Micropuncture of cultured bovine corneal endothelial cells led to registrations stable for hours. Intracellular potentials were mainly in the range of -40 to -55 mV, average 46.3 +/- 0.6 mV (SEM). Changes of extracellular [HCO-3] led to voltage transients, their amplitude depending logarithmically on [HCO-3] with a mean slope of 37.3 +/- 8.8 (SD) mV. After removal of bicarbonate/CO2, a steady-state depolarization was seen. This steady-state depolarization, but not the voltage transients, could be reduced by 1 mM Ba++. After removal of bicarbonate, the voltage response to changes of extracellular potassium was reduced. Alteration of pHi induced by permeable buffers (butyrate, glycodiazine and ammonium) also resulted in voltage transients, internal acidification being correlated with a hyperpolarization, and internal alkalinization with a depolarization. Also changes of external pH caused voltage responses, alkalinization causing a hyperpolarization, acidification a depolarization. Methazolamide, an inhibitor of carbonic anhydrase, as well as stilbenes (SITS or DIDS) caused a reduction of the voltage response to HCO-3 and pH. Their effects were additive. It is suggested that corneal endothelial cells possess one or two electrogenic transporters for HCO-3 or related species, one of which is inhibitable by stilbenes.

Animals↗

PubMed2005

Degradation and effects of the potential mosquito larvicides methazolamide and acetazolamide in sheepshead minnow (Cyprinodon variegatus).

To test for environmental persistence in order to determine the potential of carbonic anhydrase inhibitors as larvicides, the decomposition and degradation of samples containing methazolamide (MTZ) and acetazolamide (ACZ) in aqueous solution were monitored under different conditions. Additionally, nontarget species impact was assessed in an acute toxicity test using sheepshead minnow (Cyprinodon variegatus). The fish were exposed for 120 h to 10(-3) and 10(-4) M each compound in replicate seawater tanks. In the high-MTZ treatment, all fish died within 48 h, while mortality in the low-MTZ treatment was 27% at 120 h. In the high-ACZ treatment mortality reached 83% at 120 h. We observed no mortality for the lowest dose of ACZ. Tissue samples were collected from the fish to investigate absorption of the compounds. In the gills, MTZ concentrations were around 40 microg g(-1) and ACZ reached concentrations up to 80 microg g(-1). Liver concentrations were low for MTZ probably due to metabolism.

Acetazolamide↗

PubMed1995

Colour vision and side-effects during treatment with methazolamide.

The retina contains Na+K(+)-ATPase and carbonic anhydrase (CA), enzymes that regulate ion fluxes across cell membranes of photoreceptors. Since inhibition of retinal Na+K(+)-ATPase by digitalis impairs colour vision, we wanted to find out whether this also occurs after inhibition of CA. In a double-masked cross-over study with placebo, 14 male volunteers were given 50 mg q.i.d. of the CA inhibitor methazolamide for 2 weeks. A disturbance of colour discrimination was observed in 8 of the 14 subjects, in the classification phase of Lanthony New Color Test. The presence of the disturbance was not significantly correlated to the degree of acidosis or to other side-effects. Its mechanism could be interpreted as a specific effect of CA inhibition in the retina (or the visual cortex) calculated to more than 99.9%.

Adult↗

PubMed1989

Measurement of aqueous humor flow following scleral injection of sulfacetamide as marker: effect of methazolamide, timolol, and pilocarpine.

A simple technique for rapid determination of the flow of aqueous humor (AH) in rabbits is described. Data from control eyes and eyes treated with known inhibitors of aqueous humor production are presented as evidence of the suitability of the technique for comparing the influence of other drugs on aqueous flow. The flow measurement depends on marker dilution by fluid turnover during the first 30 min after 5 microliters marker solution is delivered to the anterior chamber. This is done by passing a needle through the sclera and behind the iris. The advantage of this route is that it permits withdrawal of the needle after delivery without leakage of marker or aqueous humor. Sulfacetamide (SAC), a sulfonamide with low lipid solubility and pKa 5.4, is the marker of flow used here. Control flow data from SAC, fluorescein (FL), reactive blue-2, and 14C-inulin as markers were compared. The control flow measured with SAC in two independent groups is 3.91 and 3.40 microliters/min or 3.69 +/- 0.37 S.E. overall. The data show that inhibition of carbonic anhydrase (CA) in ciliary processes by systemic methazolamide reduces flow 38%. Topical timolol reduces flow 35%. Pilocarpine, which is known to decrease IOP largely by increasing outflow facility, did not significantly reduce flow. This system for measuring AH flow allows rapid accumulation of data for topical, intracameral or systemic treatments.

Animals↗

PubMed1998

The ocular distribution of methazolamide after corneal and scleral administration: the effect of ionization state.

The accession of methazolamide in ionized and unionized form to cornea, sclera, aqueous humor and ciliary process was studied 10 minutes following separate application to either sclera or cornea of a 1 mM solution. Cornea and ciliary process concentrations were 27.3 and 14.5 microM for unionized application to cornea and 10.1 and 7.1 microM for ionized application. Bulk aqueous humor concentrations were much lower, 3.1 and 1.1 microM, and cannot account for drug found in ciliary process on this time scale. Scleral application of drug, by contrast, gave undetectable ciliary process concentrations. These results are presented as a model for drug disposition following single drop topical sulfonamide therapy. The scleral pathway for drug delivery to ciliary process was further tested by application to sclera of 300 microL of either a 1 mM ionized or unionized solution for 30 minutes or as a 2% (85.5 mM) ionized solution for 30 minutes. In these series, red cell carbonic anhydrase was presaturated at -24 hours with drug to remove a possible route for loss of drug from sclera, that of the systemic circulation and the high concentration of carbonic anhydrase in red cells. After either ionized or unionized application, approximately 1 microM was detected in ciliary process, but all drug was attributable to the blood content of the tissue and the drug bound to red cell carbonic anhydrase. After 2% dosing, 4 microM was detected in ciliary process after allowance for drug in red cells. This concentration is below that necessary for inhibition of ciliary process carbonic anhydrase, suggesting that especially with regard to topical sulfonamide therapy, the corneal route of drug delivery to ciliary process predominates greatly over the scleral route.

Animals↗

PubMed1989

Methazolamide-associated temporary leukopenia and thrombocytopenia.

A three-week course of methazolamide therapy for chronic open-angle glaucoma resulted in marked leukopenia and thrombocytopenia. Prompt discontinuation of therapy resulted in complete recovery of white blood cell and platelet counts within five days. The recommendations for patients receiving carbonic anhydrase inhibitors for blood count control at six-month intervals are discussed.

Aged↗

PubMed1999