Kaila , K & Löscher , W 2022 , ' Bumetanide for neonatal seizures : No light in the pharmacokinetic/dynamic tunnel ' , Epilepsia , vol. 63 , no. 7 , pp. 1868-1873 . https://doi.org/10.1111/epi.17279
Title: | Bumetanide for neonatal seizures : No light in the pharmacokinetic/dynamic tunnel |
Author: | Kaila, Kai; Löscher, Wolfgang |
Contributor organization: | Molecular and Integrative Biosciences Research Programme Neuroscience Center Kai Kaila / Principal Investigator Laboratory of Neurobiology University of Helsinki Helsinki Institute of Life Science HiLIFE |
Date: | 2022-07 |
Language: | eng |
Number of pages: | 6 |
Belongs to series: | Epilepsia |
ISSN: | 0013-9580 |
DOI: | https://doi.org/10.1111/epi.17279 |
URI: | http://hdl.handle.net/10138/346712 |
Abstract: | In his editorial, Kevin Staley criticizes our recent work demonstrating the lack of effect of bumetanide in a novel model of neonatal seizures. The main points in our response are that (1) our work is on an asphyxia model, not one on "hypercarbia only"; (2) clinically relevant parenteral doses of bumetanide applied in vivo lead to concentrations in the brain parenchyma that are at least an order of magnitude lower than what would be sufficient to exert any direct effect-even a transient one-on neuronal functions, including neonatal seizures; and (3) moreover, bumetanide's molecular target in the brain is the Na-K-2Cl cotransporter NKCC1, which has vital functions in neurons, astrocytes, and oligodendrocytes as well as microglia. This would make it impossible even for highly brain-permeant NKCC1 blockers to specifically target depolarizing and excitatory actions of gamma-aminobutyric acid in principal neurons of the brain, which is postulated as the rationale of clinical trials on neonatal seizures. |
Subject: |
animal models
bumetanide hypoxic-ischemic encephalopathy neonatal seizures NKCC1 CATION-CHLORIDE COTRANSPORTERS IMPERMEANT ANIONS ESTABLISH CARBON-DIOXIDE HYPOXIA BRAIN PHARMACOLOGY KCC2 PATHOPHYSIOLOGY ACCUMULATION 3112 Neurosciences 3124 Neurology and psychiatry |
Peer reviewed: | Yes |
Rights: | cc_by |
Usage restriction: | openAccess |
Self-archived version: | publishedVersion |
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