Xanomeline and trospium
Muscarinic antipsychotics
Muscarinic antipsychotics
A schizophrenia treatment that stimulates brain M1/M4 muscarinic receptors (xanomeline) while trospium blocks muscarinic effects in the body.
Quick facts
- Group
- Muscarinic antipsychotics
- Target
- Muscarinic M4 and M1 receptors (xanomeline, agonist); M4 shown
- Used for
- Schizophrenia in adults
- Key effects
- Nausea · Constipation or diarrhoea · Dry mouth
- Monitor
- Liver tests · Urination and bowel habit · Heart rate
- ATC
- N05AX50
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows xanomeline bound to the human M4 muscarinic receptor with its Gi protein. Trospium, the second component, is not in the structure.
Xanomeline is a muscarinic agonist that prefers M1 and M4 receptors and acts in the brain. M4 agonism is thought to be an antipsychotic mechanism (mice lacking M4 show a psychosis-like phenotype), and it works without blocking D2 receptors. Trospium is a quaternary antimuscarinic that hardly crosses the blood-brain barrier; it is added to limit the cholinergic effects of xanomeline in the rest of the body.
- Xanomeline stimulates brain M1 and M4 receptors
- M4 agonism is thought to calm psychosis
- Trospium blocks muscarinic receptors outside the brain
- No D2 block: little parkinsonism or prolactin rise
Indications
- Schizophrenia in adults Schizophrenia →
Adverse effects
Common
- Nausea, vomiting, heartburn and abdominal pain
- Constipation or diarrhoea
- Dry mouth, blurred vision
- Fast heart rate, dizziness, sleepiness
Contraindications
- Urinary retention or bladder outflow obstruction
- Gastric retention
- Untreated narrow-angle glaucoma
- Liver disease
- Hypersensitivity to xanomeline or trospium
Key interactions
- Other anticholinergic drugs
- More dry mouth, constipation, urinary retention and confusion
- Alcohol
- Worse side effects such as dizziness and sleepiness
What is monitored
- Liver tests
- Urination and bowel habit
- Heart rate
- Psychotic symptoms
Administration and safety
- Capsules are swallowed whole, not opened or chewed
- Given on an empty stomach, apart from meals
Pregnancy and breastfeeding
Human data are limited; use weighs benefit and risk.
Nursing care
- Asks about difficulty passing urine, weak stream or incomplete emptying
- Watches for jaundice, dark urine or abdominal pain and reports them
- Records heart rate and asks about nausea and constipation
- Takes extra care in older patients, who are more prone to side effects
Pharmacokinetics
- Absorption
- By mouth, on an empty stomach (one hour before or two hours after a meal)
- Elimination
- The trospium component is eliminated mainly by the kidneys
Test yourself
Think of the answer, then tap the question to see it.
Which receptors does xanomeline stimulate to treat schizophrenia?
Muscarinic M1 and M4 receptors in the brain.
Why does trospium not cancel xanomeline's antipsychotic effect?
Trospium is a quaternary amine that barely crosses the blood-brain barrier, so it acts mainly in the periphery.
Which urinary problem is a warning with this combination?
Urinary retention.
Connections
← Back to the class: Muscarinic antipsychotics
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Xanomeline and trospium chloride: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.