Figure 2: Pathways in the brain implicated in the clinical presentation of mefloquine toxicity. Loss of ascending inhibition within the nigrostriatal-pedunculopontine, mesolimbic and mesocortical pathways, resulting in hyperactivation of neurons in the amygdala, striatum, nucleus accumbens, and cortical and hippocampal areas, as well as within descending pathways to the Raphe nuclei, and cerebellum could give rise to the complex neuropsychiatric sequelae observed in patients exposed to prophylactic and treatment doses of mefloquine. Secondary disinhibition of striato-cortical pathways is implicated in seizure and motor and cognitive changes observed in affected individuals.