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Neuroexcitatory actions of Tamiflu and its carboxylate metabolite

Yukitoshi Izumi1, Kazuhiro Tokuda, Kazuko A O'dell

  • 1Washington University School of Medicine, Department of Psychiatry, Box 8134, 660 S Euclid Avenue, St. Louis, MO 63110, United States. izumiy@wustl.edu

Neuroscience Letters
|September 22, 2007
PubMed

Insights

Oseltamivir (Tamiflu) may affect the central nervous system, particularly when combined with alcohol. Further research is needed to understand these neuropsychiatric effects and ensure safe oseltamivir administration.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Toxicology

Background:

  • Oseltamivir (Tamiflu) is stockpiled for avian influenza (H5N1) and used for seasonal flu.
  • Adverse neuropsychiatric events and deaths linked to Tamiflu use are reported in Japan.
  • Understanding oseltamivir's central nervous system effects is crucial for safe administration.

Purpose of the Study:

  • To investigate the potential adverse effects of oseltamivir on the central nervous system.
  • To determine if oseltamivir interacts with ethanol to produce adverse effects.
  • To examine the impact of oseltamivir and its metabolite on neuronal activity.

Main Methods:

  • Systemic injection of oseltamivir in juvenile rats.
  • Assessment of behavioral responses to ethanol following oseltamivir administration.
  • Electrophysiological recordings in rat hippocampal slices (CA1 region).
  • Administration of oseltamivir and oseltamivir carboxylate to slices, with and without ethanol.

Main Results:

  • Oseltamivir altered ethanol's effects on reflex duration and body temperature.
  • Oseltamivir induced paired-pulse facilitation in hippocampal CA1 neurons.
  • Oseltamivir carboxylate facilitated neuronal firing, independent of GABAergic disinhibition.
  • Ethanol enhanced the facilitatory effects of oseltamivir carboxylate on neuronal firing.

Conclusions:

  • Oseltamivir exhibits effects on the central nervous system.
  • Combined administration of oseltamivir with other agents, like ethanol, may potentiate adverse effects.
  • Further investigation into oseltamivir's neurotoxicity and safe usage guidelines is warranted.

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