Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany.
Center for Systems Neuroscience, Hannover, Germany.
Epilepsia. 2021 Apr;62(4):941-946. doi: 10.1111/epi.16866. Epub 2021 Mar 25.
In this response to a commentary by Ben-Ari and Delpire on our recent study on the pharmacology of neonatal seizures in a novel, physiologically validated rat model of birth asphyxia, we wish to rectify their inaccurate descriptions of our model and data. Furthermore, because Ben-Ari and Delpire suggest that negative data on bumetanide from preclinical and clinical trials of neonatal seizures have few implications for (alleged) bumetanide actions on neurons in other brain disorders, we will discuss this topic as well. Based on the poor brain penetration of bumetanide, combined with the extremely wide cellular expression patterns of the target protein NKCC1, it is obvious that the numerous actions of systemically applied bumetanide described in the literature are not mediated by the drug's effects on central neurons.
在对我们最近在一种新的、生理验证的窒息性出生大鼠模型中研究新生儿癫痫发作的药理学的评论的回应中，本-阿里和德尔皮尔错误地描述了我们的模型和数据，我们希望对此进行纠正。此外，由于本-阿里和德尔皮尔认为在新生儿癫痫发作的临床前和临床试验中，布美他尼的阴性数据对（据称）布美他尼在其他脑部疾病中的神经元作用影响不大，我们也将讨论这个话题。鉴于布美他尼在脑内的穿透性差，加上其靶蛋白 NKCC1 的细胞表达模式极其广泛，很明显，文献中描述的全身性应用布美他尼的众多作用并非由该药物对中枢神经元的作用介导。
