{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:24:06Z","timestamp":1760783046571},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":273,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:p><jats:bold>Background and purpose:<\/jats:bold> Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP). Whether these drugs prevent vacuolar myopathy, which is a pathogenic factor in hypoPP, is unknown. The effects of these drugs on the efflux of lactate from skeletal muscle were also investigated.<\/jats:p><jats:p><jats:bold>Experimental approach:<\/jats:bold> For 10 days, K<jats:sup>+<\/jats:sup>\u2010depleted rats, a model of hypoPP, were administered 5.6 mg\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003day<jats:sup>\u22121<\/jats:sup> of acetazolamide, dichlorphenamide or bendroflumethiazide (the last is not an inhibitor of CA). Histological analysis of vacuolar myopathy and <jats:italic>in vitro<\/jats:italic> lactate efflux measurements were performed in skeletal muscles from treated and untreated K<jats:sup>+<\/jats:sup>\u2010depleted rats, and also from normokalemic rats.<\/jats:p><jats:p><jats:bold>Key results:<\/jats:bold> About three times as many vacuoles were found in the type II fibres of tibialis anterioris muscle sections from K<jats:sup>+<\/jats:sup>\u2010depleted rats as were found in the same muscle from normokalemic rats. In <jats:italic>ex vivo<\/jats:italic> experiments, a higher efflux of lactate on <jats:italic>in vitro<\/jats:italic> incubation was found in muscles of K<jats:sup>+<\/jats:sup>\u2010depleted rats compared with that found in muscles from normokalemic rats. After treatment of K<jats:sup>+<\/jats:sup>\u2010depleted rats with acetazolamide, the numbers of vacuoles in tibialis anterioris muscle decreased to near normal values. Incubation with acetazolamide <jats:italic>in vitro<\/jats:italic> inhibited efflux of lactate from muscles of K<jats:sup>+<\/jats:sup>\u2010depleted rats. In contrast, bendroflumethiazide and dichlorphenamide failed to prevent vacuolar myopathy after treatment <jats:italic>in vivo<\/jats:italic> and failed to inhibit lactate efflux <jats:italic>in vitro<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Conclusions and implications:<\/jats:bold> Acetazolamide prevents vacuolar myopathy in K<jats:sup>+<\/jats:sup>\u2010depleted rats. 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