Abstract:
Antipsychotics represent the mainstay of schizophrenia pharmacological therapy, and their role has been expanded in the last years to mood disorders treatment. Although introduced in 1952, many years of research were required before an accurate picture of how antipsychotics work began to emerge. Despite the well-recognized characterization of antipsychotics in typical and atypical based on their liability to induce motor adverse events, their main action at dopamine D2R to elicit the \"anti-psychotic\" effect, as well as the multimodal action at other classes of receptors, their effects on intracellular mechanisms starting with receptor occupancy is still not completely understood. Significant lines of evidence converge on the impact of these compounds on multiple molecular signaling pathways implicated in the regulation of early genes and growth factors, dendritic spine shape, brain inflammation, and immune response, tuning overall the function and architecture of the synapse. Here we present, based on PRISMA approach, a comprehensive and systematic review of the above mechanisms under a translational perspective to disentangle those intracellular actions and signaling that may underline clinically relevant effects and represent potential targets for further innovative strategies in antipsychotic therapy.
摘要:
抗精神病药物是精神分裂症药物治疗的支柱,在过去的几年里,他们的作用已经扩大到情绪障碍治疗。尽管在1952年引入,但在准确了解抗精神病药物的工作原理之前,还需要多年的研究。尽管抗精神病药物的典型和非典型特征是公认的,基于其诱发运动不良事件的责任,它们对多巴胺D2R的主要作用是引发“抗精神病药”效应,以及其他受体的多模态作用,它们对从受体占据开始的细胞内机制的影响仍未完全理解。重要的证据集中在这些化合物对涉及早期基因和生长因子调节的多个分子信号通路的影响上。树突状脊柱形状,脑部炎症,和免疫反应,全面调整突触的功能和架构。在这里,我们提出,基于PRISMA方法,从翻译的角度对上述机制进行了全面和系统的回顾,以解开那些可能强调临床相关效应的细胞内作用和信号传导,并代表了抗精神病药物治疗进一步创新策略的潜在目标。