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Furthermore, because Ben\u2010Ari 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.<\/jats:p>","DOI":"10.1111\/epi.16866","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T15:55:06Z","timestamp":1616687706000},"page":"941-946","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Reply to the commentary by Ben\u2010Ari and Delpire: Bumetanide and neonatal seizures: Fiction versus reality"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9648-8973","authenticated-orcid":false,"given":"Wolfgang","family":"L\u00f6scher","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Pharmacy University of Veterinary Medicine Hannover Germany"},{"name":"Center for Systems Neuroscience Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0668-5955","authenticated-orcid":false,"given":"Kai","family":"Kaila","sequence":"additional","affiliation":[{"name":"Molecular and Integrative Biosciences University of Helsinki Helsinki Finland"},{"name":"Neuroscience Center (HiLIFE) University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16830"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16778"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16790"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2016.00090"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13467"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057148"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70303-5"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.2165\/11596620-000000000-00000"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0633-10.2010"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24124"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.09.025"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2011.02.018"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12620"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21020591"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1983.tb02267.x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.05.045"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.02.006"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.120.019539"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-016-0554-7"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-018-0242-2"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-019-0319-6"},{"key":"e_1_2_11_23_1","volume-title":"Midazolam","author":"Lingamchetty TN","year":"2020"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3458.1998.tb00074.x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405621102"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.077495"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3819"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2013.11.004"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1301"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00017.2006"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00171-3"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2004.06.003"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1717337114"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1234-11.2011"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04459.x"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181dd25bc"},{"key":"e_1_2_11_37_1","unstructured":"SedmakG Jovanov\u2010MilosevicN PuskarjovM KailaK JudasM.Expression patterns of KCl cotransporter KCC2 in the human fetal and adult brain. 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