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

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 reuptake, promotion of release) and postsynapses (guanosine 5′-triphosphate (GTP) γS binding), using rat brain synaptosomes. Neither Tamiflu nor GS4071 influenced the re-uptake/release of the 3 monoamines or GTP binding in postsynapses. © 2007 Pharmaceutical Society of Japan.