Pejčić Ana V
Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia.
World J Psychiatry. 2025 Jun 19;15(6):105409. doi: 10.5498/wjp.v15.i6.105409.
This minireview explores the role of acetylcholine and muscarinic receptors in the pathophysiology of schizophrenia and summarizes the latest data on xanomeline/trospium chloride, a novel antipsychotic approved by the United States Food and Drug Administration in September 2024. Evidence suggests that cholinergic dysfunction, particularly an imbalance in the expression of the M1 and M4 muscarinic receptors, may contribute to the pathophysiology and symptoms of schizophrenia. Xanomeline/trospium chloride combines xanomeline, an M1 and M4 receptor agonist, with trospium chloride, a non-selective peripheral muscarinic receptor antagonist that reduces peripheral cholinergic side effects. Clinical trials have demonstrated significant reductions in the positive and negative symptoms of schizophrenia, with improvements in Positive and Negative Syndrome Scale scores observed as early as two weeks. A post-hoc analysis of one trial revealed cognitive improvements in patients with baseline cognitive impairment. This medication was generally well-tolerated, with mild-to-moderate gastrointestinal symptoms being the most common adverse events. While these results are promising, further research is needed to better understand its effectiveness and safety in real-world clinical practice, and to define its optimal role in managing this complex psychiatric disorder.
本综述探讨了乙酰胆碱和毒蕈碱受体在精神分裂症病理生理学中的作用，并总结了2024年9月美国食品药品监督管理局批准的新型抗精神病药物占诺美林/曲司氯铵的最新数据。有证据表明，胆碱能功能障碍，尤其是M1和M4毒蕈碱受体表达失衡，可能与精神分裂症的病理生理学和症状有关。占诺美林/曲司氯铵将M1和M4受体激动剂占诺美林与曲司氯铵（一种非选择性外周毒蕈碱受体拮抗剂，可减少外周胆碱能副作用）相结合。临床试验表明，精神分裂症的阳性和阴性症状显著减轻，早在两周时就观察到阳性和阴性症状量表评分有所改善。一项试验的事后分析显示，基线认知障碍患者的认知功能有所改善。这种药物总体耐受性良好，轻度至中度胃肠道症状是最常见的不良事件。虽然这些结果很有前景，但仍需要进一步研究，以更好地了解其在实际临床实践中的有效性和安全性，并确定其在治疗这种复杂精神疾病中的最佳作用。
