Luo Chao, Wang Xu, Huang Hanxue, Mao Xiaoyuan, Zhou Honghao, Liu Zhaoqian
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China.
Front Pharmacol. 2019 Apr 9;10:371. doi: 10.3389/fphar.2019.00371. eCollection 2019.
Antipsychotics are the first-line medications prescribed for patients with schizophrenia or other mental disorders. Cumulative evidence has revealed that metabolic dysfunctions frequently occur in patients receiving antipsychotics, especially second-generation antipsychotics, and these effects may decrease patient compliance and increase health costs. Metformin is an effective pharmaceutical adjuvant for ameliorating antipsychotic-induced metabolic dysfunction (AIMD) in clinical practice. However, the mechanism of the effects of metformin on AIMD remains unclear. The gut-brain axis is a bidirectional communication system between the gastrointestinal tract and the central nervous system and has been associated with many pathological and physiological conditions, such as those related to metabolism. Antipsychotics interact with and have affinity for dopamine receptors and other receptors in the brain, and treatment with these antipsychotics has been shown to influence gut microbiota metabolism and composition, as observed in both animal and human studies. Metformin exerts an antidiabetic effect that is correlated with activation of AMP-kinase in the hypothalamus, and metformin also influences gut flora. Therefore, the gut-brain axis may play a role in the effect of metformin on AIMD. Since no direct evidence is available, this perspective may provide a direction for further research.
抗精神病药物是为精神分裂症或其他精神障碍患者开的一线药物。累积证据表明，接受抗精神病药物治疗的患者，尤其是接受第二代抗精神病药物治疗的患者，经常出现代谢功能障碍，这些影响可能会降低患者的依从性并增加医疗成本。在临床实践中，二甲双胍是改善抗精神病药物引起的代谢功能障碍（AIMD）的有效药物辅助剂。然而，二甲双胍对AIMD的作用机制仍不清楚。肠-脑轴是胃肠道和中枢神经系统之间的双向通信系统，与许多病理和生理状况有关，例如与代谢相关的状况。抗精神病药物与大脑中的多巴胺受体和其他受体相互作用并对其具有亲和力，并且在动物和人体研究中均观察到，使用这些抗精神病药物进行治疗会影响肠道微生物群的代谢和组成。二甲双胍发挥抗糖尿病作用，这与下丘脑AMP激酶的激活相关，并且二甲双胍也会影响肠道菌群。因此，肠-脑轴可能在二甲双胍对AIMD的作用中发挥作用。由于尚无直接证据，这一观点可能为进一步的研究提供方向。
