Li Nana, Cao Ting, Wu Xiangxin, Tang Mimi, Xiang Daxiong, Cai Hualin
Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China.
Institute of Clinical Pharmacy, Central South University, Changsha, China.
Front Pharmacol. 2020 Feb 4;10:1669. doi: 10.3389/fphar.2019.01669. eCollection 2019.
Metabolic side effects such as weight gain and disturbed lipid metabolism are often observed in the treatment of atypical antipsychotic drugs (AAPDs), which contribute to an excessive prevalence of metabolic syndrome among schizophrenic patients. Great individual differences are observed but the underlying mechanisms are still uncertain. Research on pharmacogenomics indicates that gene polymorphisms involved in the pathways controlling food intake and lipid metabolism may play a significant role. In this review, relevant genes (, , , , , , , , , ) and genetic polymorphisms related to metabolic side effects of AAPDs especially dyslipidemia were summarized. Apart from clinical studies, and evidence is also analyzed to support related theories. The association of central and peripheral mechanisms is emphasized, enabling the possibility of using peripheral gene expression to predict the central status. Novel methodological development of pharmacogenomics is in urgent need, so as to provide references for individualized medication and further to shed some light on the mechanisms underlying AAPD-induced lipid disturbances.
在非典型抗精神病药物(AAPDs)治疗中,常观察到体重增加和脂质代谢紊乱等代谢副作用,这导致精神分裂症患者中代谢综合征的患病率过高。个体差异很大,但潜在机制仍不确定。药物基因组学研究表明,参与控制食物摄入和脂质代谢途径的基因多态性可能起重要作用。在本综述中,总结了与AAPDs代谢副作用尤其是血脂异常相关的相关基因(、、、、、、、、、)和基因多态性。除临床研究外,还分析了和证据以支持相关理论。强调了中枢和外周机制的关联,使得利用外周基因表达预测中枢状态成为可能。迫切需要药物基因组学的新方法发展,以便为个体化用药提供参考,并进一步阐明AAPD诱导脂质紊乱的潜在机制。