# Xanomeline-Trospium Chloride as a New Paradigm in the Treatment of Schizophrenia Through Muscarinic Modulation: A Renewed Hope in Psychiatric Care

**Authors:** Mohsin Raza, Jasleen Kaur

PMC · DOI: 10.7759/cureus.102250 · Cureus · 2026-01-25

## TL;DR

Xanomeline-trospium chloride is a promising new treatment for schizophrenia that targets specific brain receptors while avoiding major side effects.

## Contribution

This review highlights xanomeline-trospium chloride as a novel muscarinic modulator with improved safety and efficacy for schizophrenia.

## Key findings

- Xanomeline-trospium chloride shows clinical efficacy with minimal metabolic impact.
- The drug has a low discontinuation rate and tolerable gastrointestinal side effects.
- It is already approved for schizophrenia and may benefit treatment-resistant cases.

## Abstract

Schizophrenia remains one of the most challenging clinical issues, despite the efforts made and the number of treatments available to date. This review examines xanomeline-trospium chloride, a novel therapeutic approach to treating schizophrenia by targeting muscarinic acetylcholine receptors (mAChRs). The drug consists of xanomeline, a selective M1/M4 receptor agonist, and trospium, a peripheral muscarinic antagonist, which are used, respectively, to meet central therapeutic needs and avoid peripheral side effects. Xanomeline-trospium chloride has demonstrated clinical efficacy. Moreover, xanomeline-trospium chloride exhibited a better safety profile compared to prior agents, with no major metabolic impact and low discontinuation rates. However, studies show transient mild to moderate gastrointestinal effects.

Nevertheless, the clinical trials of this drug have shown that it is effective and well tolerated. Although xanomeline-trospium chloride is already approved for the treatment of schizophrenia, particularly for patients who need better metabolic and cognitive outcomes, future studies should aim to investigate its efficacy in treatment-resistant schizophrenia, early-stage intervention, and other neuropsychiatric disorders. This review aims to integrate the current evidence and assess the potential of xanomeline-trospium chloride as a novel therapeutic approach in the management of schizophrenia.

## Linked entities

- **Chemicals:** xanomeline (PubChem CID 60809), trospium chloride (PubChem CID 5284631)
- **Diseases:** schizophrenia (MONDO:0005090)

## Full-text entities

- **Genes:** CYP3A4 (cytochrome P450 family 3 subfamily A member 4) [NCBI Gene 1576] {aka CP33, CP34, CYP3A, CYP3A3, CYPIIIA3, CYPIIIA4}, PRL (prolactin) [NCBI Gene 5617] {aka GHA1, pPRL}, PPIG (peptidylprolyl isomerase G) [NCBI Gene 9360] {aka CARS-Cyp, CYP, SCAF10, SRCyp}, CYP2D6 (cytochrome P450 family 2 subfamily D member 6 (gene/pseudogene)) [NCBI Gene 1565] {aka CPD6, CYP2D, CYP2D7AP, CYP2D7BP, CYP2D7P2, CYP2D8P2}, CYP4F3 (cytochrome P450 family 4 subfamily F member 3) [NCBI Gene 4051] {aka CPF3, CYP4F, CYPIVF3, LTB4H}
- **Diseases:** receptor (MESH:D013734), akathisia (MESH:D017109), psychosis (MESH:D011618), gastrointestinal disturbances (MESH:D005767), agitation (MESH:D011595), urinary retention (MESH:D016055), delusions (MESH:D063726), hallucinations (MESH:D006212), EPS (MESH:D001480), dopaminergic dysfunction (MESH:D009422), cognitive impairments (MESH:D003072), dyspepsia (MESH:D004415), spectrum (MESH:C579922), dysfunction (MESH:D006331), constipation (MESH:D003248), Parkinsonism (MESH:D010302), hepatic or renal disease (MESH:D007674), dyskinesia (MESH:D004409), dry mouth (MESH:D014987), Schizophrenia (MESH:D012559), sexual (MESH:D050035), sexual dysfunction (MESH:D012735), insomnia (MESH:D007319), Alzheimer's disease (MESH:D000544), behavioral disturbances (MESH:D001523), metabolic disturbances (MESH:D024821), syncope (MESH:D013575), vomiting (MESH:D014839), bradycardia (MESH:D001919), abdominal cramping (MESH:D003085), diarrhea (MESH:D003967), cognitive and psychotic symptoms (MESH:D019954), nausea (MESH:D009325), weight gain (MESH:D015430), mood disorders (MESH:D019964)
- **Chemicals:** rifampin (MESH:D012293), EMERGENT (-), glucose (MESH:D005947), dopamine (MESH:D004298), lipid (MESH:D008055), paroxetine (MESH:D017374), Trospium Chloride (MESH:C003330), clozapine (MESH:D003024), Xanomeline (MESH:C075257), glutamate (MESH:D018698), Acetylcholine (MESH:D000109)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

26 references — full list in the complete paper: https://tomesphere.com/paper/PMC12930935/full.md

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Source: https://tomesphere.com/paper/PMC12930935