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.
Quick facts
- Group
- 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.
Mechanism of action
The figure shows lumateperone bound to the human serotonin 5-HT2A receptor (fused to a small protein for crystallisation).
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 →
- Bipolar I disorder Bipolar disorder →
- Major depressive disorder Major depressive disorder →
Adverse effects
Common
- Sleepiness and fatigue
- Dizziness, dry mouth, nausea
- Weight gain
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
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.
Connections
← Back to the class: 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 (MedlinePlus (U.S. National Library of Medicine), 2026).
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Representative model, for educational purposes only.