The ketamine analogue, 2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone (methoxetamine) has emerged as a drug of abuse. Both methoxetamine and ketamine are antagonists of glutamate N-methyl-d-asparate receptors, and several case reports show that methoxetamine produces similar schizophrenia-like symptoms and hallucinations to ketamine. Although methoxetamine is believed to change levels of dopamine, glutamate, and serotonin in the brain, few studies thus far have examined these effects. We investigated the influence of methoxetamine on dopamine and serotonin concentrations using microdialysis and high performance liquid chromatography with electrochemical detection. To reveal the effects of methoxetamine, we monitored dopamine and serotonin concentrations in several brain areas [striatum, nucleus accumbens, and prefrontal cortex (mPFC)] after an administration of 20 mg/kg of methoxetamine. We compared the effects of methoxetamine with those of ketamine using two ketamine doses. Methoxetamine increased dopamine and serotonin concentrations most robustly in the mPFC. In addition, its effects were stronger than those of ketamine at the same molar dose, suggesting that methoxetamine causes schizophrenia-like symptoms and hallucinations by increasing the dopamine and serotonin concentrations. We conclude that consumption of methoxetamine may be more dangerous than consumption of ketamine.