Anticonvulsant efficacy of phenobarbital, bumetanide, and a combination of these drugs was studied in an in vitro hippocampal rat pup (4-7 days) preparation, with recurrent seizures induced by exposure to low-Mg solution, at the Department of Neurology, Massachusetts General Hospital, Boston. The combination of phenobarbital and bumetanide abolished these experimental seizures in 70% of hippocampi and reduced their frequency and duration in the remaining 30%. The GABA-mediated outward flow of CI in immature neurons is excitatory, contributing to a poor response to GABAergic anticonvulsants such as phenobarbital and benzodiazepines. The diuretic bumetanide blocks the Na K CI transporter system and prevents the outward flow of CI ions. Alteration of CI ion transport by bumetanide facilitates the anticonvulsant action of phenobarbital in immature animal brain, providing a potential effective therapy for neonatal seizures. [1]

COMMENT. The authors propose a clinical trial of bumetanide in combination with phenobarbital in the treatment of neonates with seizures. Previous studies cited have demonstrated a low risk of side effects with bumetanide in sick infants (Sullivan JE et al. 1996). The above laboratory study and others by my colleague, Dr Sookyong Koh, recipient of the Dreiffus-Penry Epilepsy Award at the AAN meeting, April 15, have advanced our understanding of seizure mechanisms and control of epilepsy-associated behavioral changes in the young.