Bumetanide potential treatment for HypoKPP

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Neurology. 2013 Feb 20. [Epub ahead of print]
Bumetanide prevents transient decreases in muscle force in murine hypokalemic periodic paralysis.
Wu F, Mi W, Cannon SC.

Source: From the Department of Neurology and Neurotherapeutics (F.W., W.M., S.C.C.) and Program in Neuroscience (S.C.C.), UT Southwestern Medical Center, Dallas, TX.

Abstract

OBJECTIVE:

To test the hypothesis that inhibition of the Na-K-2Cl transporter with bumetanide will reduce the susceptibility to decreases in muscle force in a mouse model of hypokalemic periodic paralysis (HypoPP).

METHODS:

In vitro contraction tests were performed on soleus muscle isolated from mice with knock-in missense mutations that result in HypoPP (sodium channel NaV1.4-R669H) or hyperkalemic periodic paralysis (HyperPP; sodium channel NaV1.4-M1592V).

RESULTS:

Bumetanide prevented the development of weakness in 2 mM K(+) and also restored force during an established attack of HypoPP. Stimulation of the Na-K-2Cl transporter via induction of hyperosmolality exacerbated the weakness seen in low K(+) and was also prevented by bumetanide. Bumetanide was more efficacious than acetazolamide for preventing weakness in low K(+) conditions. Decreases in force in HyperPP muscle exposed to 10 mM K(+) were not prevented by treatment with bumetanide.

CONCLUSIONS:

The Na-K-2Cl inhibitor bumetanide was highly effective in preventing attacks of weakness in the NaV1.4-R669H mouse model of HypoPP and should be considered for management of patients with HypoPP due to sodium channel mutations. Dehydration may aggravate HypoPP by stimulating the Na-K-2Cl transporter.

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Additional information: Bumetanide Information from the FDA

 

 

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