Cerebrospinal fluid exploratory proteomics and ketamine metabolite pharmacokinetics in human volunteers after ketamine infusion

Autor: Ruin Moaddel, Cristan A. Farmer, Mani Yavi, Bashkim Kadriu, Min Zhu, Jinshui Fan, Qinghua Chen, Elin Lehrmann, Giovanna Fantoni, Supriyo De, Caio H. Mazucanti, Elia E. Acevedo-Diaz, Peixiong Yuan, Todd D. Gould, Lawrence T. Park, Josephine M. Egan, Luigi Ferrucci, Carlos A. Zarate, Jr.
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: iScience, Vol 26, Iss 12, Pp 108527- (2023)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2023.108527
Popis: Summary: Ketamine is a treatment for both refractory depression and chronic pain syndromes. In order to explore ketamine’s potential mechanism of action and whether ketamine or its metabolites cross the blood brain barrier, we examined the pharmacokinetics of ketamine and its metabolites—norketamine (NK), dehydronorketamine (DHNK), and hydroxynorketamines (HNKs)—in cerebrospinal fluid (CSF) and plasma, as well as in an exploratory proteomic analysis in the CSF of nine healthy volunteers who received ketamine intravenously (0.5 mg/kg IV). We found that ketamine, NK, and (2R,6R;2S,6S)-HNK readily crossed the blood brain barrier. Additionally, 354 proteins were altered in the CSF in at least two consecutive timepoints (p
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