[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Second-generation antipsychotics](https://durgical.com/en/pharmacology/classes/second-generation-antipsychotics/) › Lumateperone

# Lumateperone

## Second-generation antipsychotics?

Second-generation antipsychotics

An atypical antipsychotic with much stronger 5-HT2A than D2 binding: little effect on prolactin. Used in schizophrenia, bipolar I disorder and depression.

Updated Nov 1, 2026

## Quick facts

**Group**
[Second-generation antipsychotics](https://durgical.com/en/pharmacology/classes/second-generation-antipsychotics/)

**Target**
Serotonin 5-HT2A receptor (antagonist), with weaker dopamine D2 action

**Used for**
Schizophrenia · Bipolar I disorder

**Key effects**
Sleepiness and fatigue · Dizziness · Weight gain

**Monitor**
Weight · Mood and suicidal thoughts

No doses: the clinician sets them by the current guideline.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

◎**Serotonin 5-HT2A receptor (antagonist), with weaker dopamine D2 action**Lumateperone

ⓘ The figure shows lumateperone bound to the human serotonin 5-HT2A receptor (fused to a small protein for crystallisation).

**Target in 3D:** Serotonin 5-HT2A receptor (antagonist), with weaker dopamine D2 action. PDB structure 7WC8 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/7WC8) · Drag to rotate · pinch to zoom

Lumateperone binds serotonin 5-HT2A receptors far more tightly than dopamine D2 receptors. Its antipsychotic effect relies more on 5-HT2A antagonism (together with dopamine D1-related effects) than on strong D2 blockade, so it causes very little prolactin rise. It is cleared mainly by CYP3A4, so inducers make it ineffective and strong inhibitors raise its levels.

- Lumateperone strongly blocks 5-HT2A
- Weaker D2 action than most antipsychotics
- Little prolactin rise
- CYP3A4 controls its levels

## Indications

- Schizophrenia [Schizophrenia →](https://durgical.com/en/conditions/schizophrenia/)
- Bipolar I disorder [Bipolar disorder →](https://durgical.com/en/conditions/bipolar-disorder/)
- Major depressive disorder [Major depressive disorder →](https://durgical.com/en/conditions/major-depressive-disorder/)

## Adverse effects

### Common

- Sleepiness and fatigue
- Dizziness, dry mouth, nausea
- Weight gain

### Serious (rare, important)

- Higher mortality in older people with dementia-related psychosis (boxed warning)
- Suicidal thoughts in young people treated for depression (boxed warning)
- Neuroleptic malignant syndrome; tardive dyskinesia
- Hyperglycaemia; low white cell count; seizures; orthostatic hypotension and falls

## Contraindications

- Hypersensitivity to lumateperone

## Key interactions

**CYP3A4 inducers (rifampicin, carbamazepine, St John's wort)**
Avoided: lumateperone levels fall almost completely

**Strong or moderate CYP3A4 inhibitors (itraconazole, diltiazem) and grapefruit**
Several-fold higher exposure; grapefruit is avoided

**UGT inhibitors such as valproate**
Higher lumateperone exposure

**Alcohol**
Added sleepiness

## What is monitored

- Weight, glucose and lipids
- Mood and suicidal thoughts in young people
- Abnormal movements

## Administration and safety

- Every new medicine and herbal product is checked for CYP3A4 effects
- No grapefruit or grapefruit juice during treatment

## Pregnancy and breastfeeding

Human data are limited; it may also reduce fertility in men and women.

## Nursing care

- Records weight, glucose and lipids at baseline and during treatment
- Asks about St John's wort and other supplements
- Watches for sleepiness, dizziness on standing and falls
- Teaches the patient and family to report suicidal thoughts or worsening mood

## Pharmacokinetics

**Absorption**
Taken by mouth; very low oral bioavailability (about 4%)

**Metabolism**
Mainly CYP3A4, with UGT enzymes in later steps

## Memory aid

«LUMAteperone LIGHTS up 2A, dims D2 only a little»: little prolactin, but CYP3A4 holds the switch.

## Test yourself

Think of the answer, then tap the question to see it.

## Which receptor does lumateperone bind much more strongly than D2?

The serotonin 5-HT2A receptor.

## Why is lumateperone avoided with rifampicin or carbamazepine?

These CYP3A4 inducers lower its levels almost completely.

## How does lumateperone affect prolactin compared with risperidone?

It has almost no effect on prolactin, whereas risperidone raises it markedly.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/lumateperone/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## Connections

## Related drugs 2

- [Quetiapine](https://durgical.com/en/pharmacology/quetiapine/)
- [Pimavanserin](https://durgical.com/en/pharmacology/pimavanserin/)

## Related conditions 3

- [Schizophrenia](https://durgical.com/en/conditions/schizophrenia/)
- [Bipolar disorder](https://durgical.com/en/conditions/bipolar-disorder/)
- [Major depressive disorder](https://durgical.com/en/conditions/major-depressive-disorder/)

[← Back to the class: Second-generation antipsychotics](https://durgical.com/en/pharmacology/classes/second-generation-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: [Lumateperone: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a620014.html) (MedlinePlus (U.S. National Library of Medicine), 2026).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/lumateperone/