156. Antipsychotic regulation of signal transduction pathways

Abstract

Despite forty years of investigation, the mechanism of action of antipsychotic medications is not well known. The initial characterization of antipsychotics revealed modulatory effects on dopaminergic pathways, but recent work has indicated effects upon multiple neurotransmitter systems. These receptor-mediated effects of antipsychotic medications converge on multiple signaling pathways. Modulation of cyclic nucleotide and phosphoinositide signaling has been directly linked to receptors targeted by antipsychotic medications. Despite the breadth of previous work, mechanistic formulation of the molecular effects of antipsychotic medications on signal transduction pathways has not been well synthesized. A review of the relevant literature for antipsychotic regulation of signaling processes will be presented. Specific differences between typical and atypical antipsychotics will be highlighted. Where relevant, molecular signaling processes will be linked to both therapeutic and adverse effects of antipsychotic medications. Finally, a model integrating different receptor families and signal transduction pathways with gene expression and clinical outcomes will be synthesized. This model will assist in the formulation of future studies examining the effects of typical and atypical antipsychotics on signaling pathways.