Is It Safe to Use a Diuretic to Treat Seizures Early in Development?

There has been considerable interest in using bumetanide, a diuretic chloride importer NKCC1 antagonist, to reduce intracellular chloride ([Cl-](i)) in epileptic neurons, thereby shifting the polarity of GABA from excitatory to inhibitory and ameliorating the actions of GABA-acting antiepileptic drugs. However, a recent study raises the important issue of potential deleterious actions of bumetanide on immature neurons, because reduction of (Cl-)(i) also alleviates a major source of excitation in developing neurons, upon which GABA exerts a trophic action. This review considers the importance of separating intrauterine from postnatal effects of bumetanide in normal versus pathologic neurons.