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However, the exact cellular and network basis of their therapeutic action is not fully understood.<\/jats:p><jats:p><jats:bold>Method:\u2002<\/jats:bold> To review the mechanism of action of antipsychotic drugs with a particular emphasis on their action in the prefrontal cortex (PFC).<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> The PFC controls a large number of higher brain functions altered in schizophrenia. Histological studies indicate the presence of a large proportion of PFC neurons expressing monoaminergic receptors sensitive to the action of atypical\u2010 and to a lesser extentclassical antipsychotic drugs. Functional studies also indicate that both drug families act at PFC level.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> Atypical antipsychotic drugs likely exert their therapeutic activity by a preferential action on PFC neurons, thus modulating the PFC output to basal ganglia circuits. 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