The loop diuretic bumetanide has been proposed previously as an adjunct treatment for neonatal seizures because bumetanide is thought to potentiate the action of γ‐aminobutyric acid (GABA)ergic drugs such as phenobarbital by preventing abnormal intracellular accumulation of chloride and the subsequent "GABA shift." However, a clinical trial in neonates failed to demonstrate such a synergistic effect of bumetanide, most likely because this drug only poorly penetrates into the brain. This prompted us to develop lipophilic prodrugs of bumetanide, such as the N,N‐dimethylaminoethyl ester of bumetanide (DIMAEB), which rapidly enter the brain where they are hydrolyzed by esterases to the parent compound, as demonstrated previously by us in adult rodents. However, it is not known whether esterase activity in neonates is sufficient to hydrolyze ester prodrugs such as DIMAEB.

中文翻译：

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布美他尼酯前药DIMAEB通过新生人和大鼠血清和新生大鼠脑中的酯酶水解生物转化为布美他尼——新生儿癫痫的新治疗策略？

环利尿剂布美他尼以前曾被提议作为新生儿癫痫发作的辅助治疗，因为布美他尼被认为通过防止细胞内氯化物异常积累和随后的“GABA 转移”来增强 γ-氨基丁酸 (GABA) 能药物如苯巴比妥的作用。 ” 然而，一项新生儿临床试验未能证明布美他尼的这种协同作用，很可能是因为这种药物很难渗透到大脑中。这促使我们开发了布美他尼的亲脂性前药，例如布美他尼的 N,N-二甲氨基乙酯 (DIMAEB)，它们迅速进入大脑，在那里它们被酯酶水解为母体化合物，正如我们之前在成年啮齿动物中所证明的那样。然而，