A history of diuretic use has been shown to be protective for first unprovo
ked seizure in adult patients. Recent animal studies suggest that certain d
iuretics have anticonvulsant activity. We evaluated the potential for the a
nticonvulsant activity of current diuretic use in a population-based, case-
control study in older adults. We also tested chlorthiazide and furosemide
for seizure protection in animal models of epilepsy. Concurrent medical pre
scription of any diuretic was protective for the development of epilepsy [o
dds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.39-0.99]. A protect
ive effect for current thiazide use was observed (OR = 0.53, CI = 0.31-0.90
), and a protective effect for furosemide was suggested (OR = 0.44, CI = 0.
1-1.9). In mice, both chlorthiazide and furosemide suppressed the occurrenc
e of maximal electroshock-induced seizures in a dose-dependent manner. Chlo
rthiazide's toxic dose for 50% of animals tested (TD50) could not be achiev
ed even with dosing as high as 1,500mg/kg for furosemide; TD50 was 549 mg/k
g. Results were similar in rats. Furosemide and chlorthiazide are protectiv
e for unprovoked seizures in an epidemiological study and in animal models.
Given the potential therapeutic value for seizure control, low toxicity, a
nd low cost, therapeutic efficacy should be explored in clinical studies.