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Current Findings and Potential Mechanisms of KarXT (Xanomeline-Trospium) in Schizophrenia Treatment.
- Source :
-
Clinical drug investigation [Clin Drug Investig] 2024 Jul; Vol. 44 (7), pp. 471-493. Date of Electronic Publication: 2024 Jun 21. - Publication Year :
- 2024
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Abstract
- Standard schizophrenia treatment involves antipsychotic medications that target D2 dopamine receptors. However, these drugs have limitations in addressing all symptoms and can lead to adverse effects such as motor impairments, metabolic effects, sedation, sexual dysfunction, cognitive impairment, and tardive dyskinesia. Recently, KarXT has emerged as a novel drug for schizophrenia. KarXT combines xanomeline, a muscarinic receptor M1 and M4 agonist, with trospium, a nonselective antimuscarinic agent. Of note, xanomeline can readily cross blood-brain barrier (BBB) and, thus, enter into the brain, thereby stimulating muscarinic receptors (M1 and M4). By doing so, xanomeline has been shown to target negative symptoms and potentially improve positive symptoms. Trospium, on the other hand, is not able to cross BBB, thereby not affecting M1 and M4 receptors; instead, it acts as an antimuscarinic agent and, hence, diminishes peripheral activity of muscarinic receptors to minimize side effects probably stemming from xanomeline in other organs. Accordingly, ongoing clinical trials investigating KarXT's efficacy in schizophrenia have demonstrated positive outcomes, including significant improvements in the Positive and Negative Syndrome Scale (PANSS) total score and cognitive function compared with placebo. These findings emphasize the potential of KarXT as a promising treatment for schizophrenia, providing symptom relief while minimizing side effects associated with xanomeline monotherapy. Despite such promising evidence, further research is needed to confirm the efficacy, safety, and tolerability of KarXT in managing schizophrenia. This review article explores the current findings and potential mechanisms of KarXT in the treatment of schizophrenia.<br /> (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
- Subjects :
- Humans
Muscarinic Antagonists therapeutic use
Muscarinic Antagonists adverse effects
Pyridines therapeutic use
Pyridines adverse effects
Pyridines pharmacology
Benzilates therapeutic use
Benzilates adverse effects
Drug Combinations
Animals
Muscarinic Agonists therapeutic use
Muscarinic Agonists adverse effects
Thiadiazoles therapeutic use
Thiadiazoles adverse effects
Thiadiazoles pharmacology
Schizophrenia drug therapy
Antipsychotic Agents therapeutic use
Antipsychotic Agents adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1179-1918
- Volume :
- 44
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Clinical drug investigation
- Publication Type :
- Academic Journal
- Accession number :
- 38904739
- Full Text :
- https://doi.org/10.1007/s40261-024-01377-9