F Artigas1. 1. Department of Neurochemistry and Neuropharmacology, Institut d' Investigacions Biomèdiques de Barcelona (CSIC), IDIBAPS,08036 Barcelona, Spain. fapnqi@iibb.csic.es
Abstract
OBJECTIVE: At therapeutic doses, classical antipsychotic drugs occupy a large proportion of subcortical dopamine D2 receptors, whereas atypical antipsychotics preferentially occupy cortical 5-HT(2) receptors. However, the exact cellular and network basis of their therapeutic action is not fully understood. METHOD: To review the mechanism of action of antipsychotic drugs with a particular emphasis on their action in the prefrontal cortex (PFC). RESULTS: 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- and to a lesser extentclassical antipsychotic drugs. Functional studies also indicate that both drug families act at PFC level. CONCLUSION: Atypical antipsychotic drugs likely exert their therapeutic activity by a preferential action on PFC neurons, thus modulating the PFC output to basal ganglia circuits. Classical antipsychotics also interact with these PFC targets in addition to blocking massively striatal D2 receptors.
OBJECTIVE: At therapeutic doses, classical antipsychotic drugs occupy a large proportion of subcortical dopamine D2 receptors, whereas atypical antipsychotics preferentially occupy cortical 5-HT(2) receptors. However, the exact cellular and network basis of their therapeutic action is not fully understood. METHOD: To review the mechanism of action of antipsychotic drugs with a particular emphasis on their action in the prefrontal cortex (PFC). RESULTS: 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- and to a lesser extentclassical antipsychotic drugs. Functional studies also indicate that both drug families act at PFC level. CONCLUSION: Atypical antipsychotic drugs likely exert their therapeutic activity by a preferential action on PFC neurons, thus modulating the PFC output to basal ganglia circuits. Classical antipsychotics also interact with these PFC targets in addition to blocking massively striatal D2 receptors.
Authors: Anniek K D Visser; Erik F J De Vries; Nisha K Ramakrishnan; Antoon T M Willemsen; Fokko J Bosker; Johan A den Boer; Rudi A J O Dierckx; Aren van Waarde Journal: Mol Imaging Biol Date: 2013-12 Impact factor: 3.488
Authors: Aine M Duffy; Megan L Fitzgerald; June Chan; Danielle C Robinson; Teresa A Milner; Kenneth Mackie; Virginia M Pickel Journal: Synapse Date: 2011-12 Impact factor: 2.562
Authors: Sheena F Owens; Marco M Picchioni; Ulrich Ettinger; Colm McDonald; Muriel Walshe; Anne Schmechtig; Robin M Murray; Fruhling Rijsdijk; Timothea Toulopoulou Journal: Brain Date: 2012-06-12 Impact factor: 13.501