[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/) › Paliperidone

# Paliperidone

## Second-generation antipsychotics?

Second-generation antipsychotics

The active metabolite of risperidone, given as an extended-release tablet or a long-acting injection for schizophrenia and schizoaffective disorder.

Updated Nov 12, 2026

Also called: 9-hydroxyrisperidone

## Quick facts

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

**Target**
Dopamine D2 and serotonin 5-HT2A receptors

**Used for**
Schizophrenia in adults and adolescents

**Key effects**
Restlessness · Sleepiness · Weight gain

**Monitor**
Weight · Movement disorders · Kidney function

**ATC**
N05AX13

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

◎**Dopamine D2 and serotonin 5-HT2A receptors**Paliperidone

ⓘ The figure shows risperidone in the human D2 receptor; paliperidone is risperidone with one added hydroxyl group and blocks the same site.

**Target in 3D:** Dopamine D2 and serotonin 5-HT2A receptors. PDB structure 6CM4 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/6CM4) · Drag to rotate · pinch to zoom

Paliperidone is 9-hydroxyrisperidone, the main active metabolite of risperidone. Like risperidone it blocks dopamine D2 receptors in the mesolimbic pathway, which reduces hallucinations and delusions, and blocks serotonin 5-HT2A receptors, which lessens extrapyramidal effects at usual doses. D2 block in the pituitary raises prolactin; alpha-1 and H1 block cause orthostatic dizziness and sedation.

- Blocks D2 receptors in mesolimbic pathways
- Blocks 5-HT2A receptors, easing motor side effects
- Positive psychotic symptoms decrease
- Pituitary D2 block raises prolactin

## Indications

- Schizophrenia in adults and adolescents [Schizophrenia →](https://durgical.com/en/conditions/schizophrenia/)
- Schizoaffective disorder in adults

## Adverse effects

### Common

- Restlessness (akathisia), stiffness, slow movement
- Sleepiness, headache
- Weight gain
- Breast enlargement or discharge, missed periods, sexual problems (raised prolactin)
- Dizziness on standing

### Serious (rare, important)

- Higher death and stroke risk in older people with dementia (boxed warning)
- Neuroleptic malignant syndrome: fever, rigidity, confusion, unstable pulse
- Tardive dyskinesia
- QT prolongation; high blood sugar; low white-cell counts; priapism

## Contraindications

- Hypersensitivity to paliperidone or risperidone
- Behavioural problems of dementia (not approved)

## Key interactions

**Other QT-prolonging drugs**
Added QT prolongation.

**CYP3A4/P-glycoprotein inducers (carbamazepine, rifampicin)**
Lower paliperidone levels; the dose may need changing.

**Alcohol and other CNS depressants**
More drowsiness.

## What is monitored

- Weight, waist, glucose and lipids
- Movement disorders (abnormal involuntary movements)
- Prolactin-related symptoms
- Kidney function; ECG when there are cardiac risks

## Administration and safety

- Extended-release tablet once daily in the morning, swallowed whole, never split, chewed or crushed.
- The empty tablet shell may appear in the stool; this is expected.
- Avoided in severe narrowing of the gut, because the tablet does not deform.
- The long-acting injection is given intramuscularly by a health worker on a fixed schedule.

## Pregnancy and breastfeeding

Newborns exposed in the third trimester may have extrapyramidal or withdrawal symptoms; use weighs benefit and risk.

## Nursing care

- Before: record weight, blood pressure, glucose, lipids and kidney function.
- During: watch for stiffness, restlessness, abnormal movements and fever.
- Teach to rise slowly, avoid overheating and avoid alcohol.
- Ask about breast changes, periods and sexual function.

## Pharmacokinetics

**Absorption**
Extended-release tablet releases the drug through the day; also a monthly or longer-acting intramuscular injection (palmitate).

**Elimination**
The dose is reduced in kidney impairment; not recommended when kidney function is very low.

## Memory aid

PALIperidone is risperidone's PAL: the same drug plus one hydroxyl, cleared by the kidneys.

## Test yourself

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

## What is the relationship between paliperidone and risperidone?

Paliperidone is 9-hydroxyrisperidone, risperidone's main active metabolite.

## Why is paliperidone's dose reduced in kidney disease?

It is cleared mainly by the kidneys, so levels rise when kidney function falls.

## Which hormone rises with paliperidone, and what symptoms follow?

Prolactin: breast enlargement or discharge, missed periods and sexual dysfunction.

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

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

## Connections

## Related drugs 3

- [Risperidone](https://durgical.com/en/pharmacology/risperidone/)
- [Aripiprazole](https://durgical.com/en/pharmacology/aripiprazole/)
- [Haloperidol](https://durgical.com/en/pharmacology/haloperidol/)

## Related conditions 1

- [Schizophrenia](https://durgical.com/en/conditions/schizophrenia/)

[← 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: [Paliperidone: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a607005.html) (MedlinePlus (U.S. National Library of Medicine), 2025); [PALIPERIDONE tablet, extended release](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=018cf3ca-bee9-23a6-e063-6394a90ad905) (DailyMed (U.S. National Library of Medicine), 2026); [Structure of the D2 Dopamine Receptor Bound to the Atypical Antipsychotic Drug Risperidone](https://www.rcsb.org/structure/6CM4) (RCSB Protein Data Bank, 2018); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N05AX13) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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