Three patients with Hypokalemic Periodic Paralysis (HOPP)-associated progressive 
interattack muscle weakness, who became unresponsive or worsened by 
acetazolamide, responded favorably to dichlorophenamide, a more potent carbonic 
anhydrase inhibitor. Dichlorophenamide in single-blind placebo-controlled 
trials, considerably improved functional strength in two of the patients and had 
a moderate but definite effect in the third. Muscle groups graded 4/5 (MRC 
scale)returned to normal; very weak (0-3/5) atrophic muscles, improved to a 
minor degree. In one patient with acetazolamide-resistant paralytic attacks, 
dichlorophenamide also diminished the frequency and severity of the acute 
attacks. Dichlorophenamide had, in the present study, less effect than 
acetazolamide in reducing serum HCO3(-) and elevating Cl-. Its effectiveness may 
be related to the degree of sensitivity of certain HOPP patients to alterations 
of Cl- and/or HCO3(-) serum levels or to a different action of the drug 
unrelated to carbonic anhydrase inhibition or acidosis. Dichlorophenamide should 
be considered as an alternate to acetazolamide in the treatment of patients with 
HOPP-associated interattack muscle weakness who have become unresponsive or 
worsened by acetazolamide.