Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

The New Horizon of Antipsychotics beyond the Classic Dopaminergic Hypothesis—The Case of the Xanomeline-Trospium Combination: A Systematic Review

Version 1 : Received: 15 April 2024 / Approved: 15 April 2024 / Online: 15 April 2024 (14:36:30 CEST)

How to cite: Vasiliu, O.; Budeanu, B.; Catanescu, M.S. The New Horizon of Antipsychotics beyond the Classic Dopaminergic Hypothesis—The Case of the Xanomeline-Trospium Combination: A Systematic Review. Preprints 2024, 2024040971. https://doi.org/10.20944/preprints202404.0971.v1 Vasiliu, O.; Budeanu, B.; Catanescu, M.S. The New Horizon of Antipsychotics beyond the Classic Dopaminergic Hypothesis—The Case of the Xanomeline-Trospium Combination: A Systematic Review. Preprints 2024, 2024040971. https://doi.org/10.20944/preprints202404.0971.v1

Abstract

Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline-trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer’s disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected 21 sources referring to 14 studies focused on KarXT, out of which only four have published results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline-trospium are good, but more data is needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.

Keywords

xanomeline; trospium; schizophrenia; Alzheimer’s disorder; psychoses; acetylcholine; muscarinic receptors; antipsychotics; dopaminergic hypothesis

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.