The antidepressant-like effect and proposed mechanism of action of TPN672MA, a novel serotonin-dopamine receptor modulator for the treatment of schizophrenia

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior Pub Date : 2024-06-25 DOI:10.1016/j.pbb.2024.173809

Jiaxin Cheng , Chunhui Wu , Yu Wang , Zhen Wang , Yang He , Jingshan Shen

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引用次数: 0

Abstract

TPN672MA, an innovative antipsychotic drug candidate currently in clinical trials, acts as a dopamine D₂/D₃ receptor partial agonist, serotonin 5-HT_1A receptor agonist, and serotonin 5-HT_2A receptor antagonist. Preclinical investigations have demonstrated its potential in treating the core symptoms of schizophrenia. The present study highlights TPN672MA’s significant antidepressant-like effects in classical behavioral models, such as the chronic social defeat stress paradigm. The pronounced 5-HT_1A receptor agonism and D₂/D₃ receptor partial agonism of TPN672MA likely contribute to its therapeutic effects in depression. Additionally, TPN672MA’s antidepressant-like efficacy may be linked to its ability to enhance the expression levels of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein-95 (PSD95) in the hippocampus. Furthermore, TPN672MA displayed a more rapid onset of antidepressant-like action. In conclusion, TPN672MA represents a promising new drug candidate for the treatment of symptoms of schizophrenia and depression.

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用于治疗精神分裂症的新型 5-羟色胺-多巴胺受体调节剂 TPN672MA 的抗抑郁样作用和拟议作用机制。

TPN672MA 是一种创新型抗精神病候选药物，目前正在进行临床试验，它是多巴胺 D2/D3 受体部分激动剂、5-羟色胺 5-HT1A 受体激动剂和 5-HT2A 受体拮抗剂。临床前研究表明，它具有治疗精神分裂症核心症状的潜力。本研究强调了 TPN672MA 在经典行为模型（如慢性社会失败压力范式）中显著的抗抑郁样作用。TPN672MA 对 5-HT1A 受体的明显激动作用和对 D2/D3 受体的部分激动作用很可能有助于其对抑郁症的治疗效果。此外，TPN672MA的抗抑郁类疗效可能与其能够提高海马中脑源性神经营养因子（BDNF）和突触后密度蛋白-95（PSD95）的表达水平有关。此外，TPN672MA 的抗抑郁作用起效更快。总之，TPN672MA 是治疗精神分裂症和抑郁症状的一种很有前途的候选新药。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacology Biochemistry and Behavior 医学-行为科学

CiteScore

6.40

自引率

2.80%

发文量

122

审稿时长

38 days

期刊介绍： Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.