Pejčić AV. Targeting muscarinic receptors in schizophrenia treatment: Novel antipsychotic xanomeline/trospium chloride. World J Psychiatry 2025; 15(6): 105409 [DOI: 10.5498/wjp.v15.i6.105409]
Corresponding Author of This Article
Ana V Pejčić, PhD, Assistant Professor, Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, Kragujevac 34000, Serbia. anapejcic201502@yahoo.com
Research Domain of This Article
Psychiatry
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Psychiatry. Jun 19, 2025; 15(6): 105409 Published online Jun 19, 2025. doi: 10.5498/wjp.v15.i6.105409
Targeting muscarinic receptors in schizophrenia treatment: Novel antipsychotic xanomeline/trospium chloride
Ana V Pejčić
Ana V Pejčić, Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
Author contributions: Pejčić AV was responsible for conception, design, literature search, formal analysis, drafting and editing of the manuscript, and approved the final manuscript. The author has read and approved the final manuscript.
Conflict-of-interest statement: Author declares no conflict of interests for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ana V Pejčić, PhD, Assistant Professor, Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, Kragujevac 34000, Serbia. anapejcic201502@yahoo.com
Received: January 21, 2025 Revised: April 4, 2025 Accepted: May 13, 2025 Published online: June 19, 2025 Processing time: 128 Days and 16.2 Hours
Abstract
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.
Core Tip: Xanomeline/trospium chloride is a potential new treatment option for a wide range of schizophrenia symptoms, offering a relatively favorable tolerability and safety profile. However, additional research is required to better understand its effectiveness and safety in real-world clinical practice, and to define its optimal role in managing this complex psychiatric disorder. As new evidence emerges, it is vital to evaluate it critically.
