Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels.

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Tricarico D, Mele A, Conte Camerino D

Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels.

Neuromuscul Disord. 2006 Jan;16(1):39-45. doi: 10.1016/j.nmd.2005.10.005. Epub 2005 Dec 20.

PubMed ID

16368240 [ View in PubMed

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Abstract

Carbonic-anhydrase inhibitors are effective in channelopathies possibly by opening the Ca2+-activated-K+ channels. However, the in vivo effects of these drugs in K+-deficient rats, the animal model of familial hypokalaemic periodic paralysis(hypokalaemic-PP), are currently unknown. Measures of insulin-responses, serum electrolytes levels and patch-clamp experiments were therefore performed in K+ -deficient rats treated in vivo with dichlorphenamide (DCP), ethoxzolamide (ETX), hydrochlorthiazide (HCT), methazolamide (MTZ), bendroflumethiazide (BFT) and acetazolamide (ACTZ). Ten days treatments of K+-deficient rats with DCP, BFT, ETX and ACTZ (5.6 mg/kg per day) restored the serum [K+] to control values and prevented the insulin-induced paralysis. In ex vivo experiments, the carbonic-anhydrase inhibitors enhanced the activity of Ca2+-activated-K+ channels with the order of efficacy: ACTZ>BFT>ETX>DCP. In contrast, HCT and MTZ failed to stimulate the Ca2+-activated-K+ channels and to prevent the hypokalaemia and paralysis. At the concentration of 1mg/kg per day, all these drugs failed to ameliorate the hypokalaemic-PP symptoms. The activation of Ca2+-activated-K+ channel in addition to the mild diuretic effect explained the efficacy of ACTZ and DCP in K+ -deficient rats and in familial hypokalaemic-PP.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Bendroflumethiazide	Carbonic anhydrase 1	Protein	Humans	Unknown	Inhibitor	Details
Bendroflumethiazide	Carbonic anhydrase 2	Protein	Humans	Unknown	Inhibitor	Details
Bendroflumethiazide	Carbonic anhydrase 4	Protein	Humans	Unknown	Inhibitor	Details