Oseltamivir (Tamiflu), a neuraminidase inhibitor, is widely used for treatment 
of influenza. Because abnormal behaviors have been observed in some Japanese 
teenagers following oseltamivir use, its safety has been questioned. Oseltamivir 
is known to alter neuronal function and behavior in animals, particularly when 
administered in combination with ethanol. Based on this, it has been 
hypothesized that interactions of oseltamivir with other drugs may result in 
altered CNS excitability in this study. It has been found that injection of 
ephedrine and caffeine overcame inactivity induced by oseltamivir and ethanol 
but did not alter changes in novelty seeking behavior in a Y-maze test. In 
ex-vivo hippocampal slices, oseltamivir carboxylate (OTC), an active form of 
oseltamivir, alters excitability in the absence of ethanol. In slices pretreated 
with OTC, long-term depression (LTD), a form of synaptic plasticity that is 
correlated with Y-maze performance was not altered if caffeine or ephedrine was 
administered individually. However, LTD could not be induced in slices 
pretreated with OTC if caffeine and ephedrine were administered simultaneously. 
These observations suggest that combination of oseltamivir with other 
neurostimulants may alter synaptic plasticity and this may contribute to 
behavioral changes associated with the drug.