Effects of oseltamivir phosphate (Tamiflu) and its metabolite (GS4071) on monoamine neurotransmission in the rat brain

Biol Pharm Bull. 2007 Sep;30(9):1816-8. doi: 10.1248/bpb.30.1816.

Abstract

As abnormal behaviors such as jumping and falling from balcony were reported in patients aged 10 to 19 years who administrated oseltamivir phosphate (Tamiflu) for treatment influenza infection, the Ministry of Health, Labor and Welfare in Japan notified that, as a rule, Tamiflu should not be prescribed to patients aged 10 to 19 years. To examine the relationship between Tamiflu and abnormal behaviors, we investigated the effects of Tamiflu and its carboxylic acid metabolite, GS4071, on the central nervous system, that is, on 3 neurotransmitters (dopamine, serotonin, and norepinephrine) in presynapses (inhibition of re-uptake, promotion of release) and postsynapses (guanosine 5'-triphosphate (GTP) gammaS binding), using rat brain synaptosomes. Neither Tamiflu nor GS4071 influenced the re-uptake/release of the 3 monoamines or GTP binding in postsynapses.

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Animals
  • Antiviral Agents / pharmacology*
  • Biogenic Monoamines / physiology*
  • Brain Chemistry / drug effects*
  • Dopamine / metabolism
  • Dopamine Uptake Inhibitors / pharmacology
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Guanosine Triphosphate / metabolism
  • In Vitro Techniques
  • Male
  • Norepinephrine / metabolism
  • Oseltamivir / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism
  • Serotonin Uptake Inhibitors / pharmacology
  • Synaptic Transmission / drug effects*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism

Substances

  • Adrenergic Uptake Inhibitors
  • Antiviral Agents
  • Biogenic Monoamines
  • Dopamine Uptake Inhibitors
  • Serotonin Uptake Inhibitors
  • Oseltamivir
  • Serotonin
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Guanosine Triphosphate
  • Dopamine
  • Norepinephrine