Identification of New Ketamine Metabolites and Their Detailed Distribution in the Mammalian Brain

Theodosia Vallianatou, Carina de Souza Anselmo, Ioanna Tsiara, Nicholas B. Bèchet, Iben Lundgaard, Daniel Globisch

Research output: Contribution to journalArticlepeer-review


Ketamine is a common anesthetic used in human and veterinary medicine. This drug has recently received increased medical and scientific attention due to its indications for neurological diseases. Despite being applied for decades, ketamine’s entire metabolism and pharmacological profile have not been elucidated yet. Therefore, insights into the metabolism and brain distribution are important toward identification of neurological effects. Herein, we have investigated ketamine and its metabolites in the pig brain, cerebrospinal fluid, and plasma using mass spectrometric and metabolomics analysis. We discovered previously unknown metabolites and validated their chemical structures. Our comprehensive analysis of the brain distribution of ketamine and 30 metabolites describes significant regional differences detected mainly for phase II metabolites. Elevated levels of these metabolites were identified in brain regions linked to clearance through the cerebrospinal fluid. This study provides the foundation for multidisciplinary studies of ketamine metabolism and the elucidation of neurological effects by ketamine.

Original languageEnglish
Pages (from-to)1335-1341
Number of pages7
JournalACS Chemical Neuroscience
Issue number7
Publication statusPublished - 2024 Apr

Subject classification (UKÄ)

  • Pharmaceutical Sciences

Free keywords

  • brain distribution
  • drug metabolism
  • Ketamine
  • mass spectrometry
  • phase II metabolites


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