[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/) › Asenapine

# Asenapine

## Second-generation antipsychotics?

Second-generation antipsychotics

A sublingual atypical antipsychotic for schizophrenia and bipolar I mania. Swallowed, it is almost inactive; it numbs the mouth.

Updated Nov 1, 2026

## Quick facts

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

**Target**
Dopamine D2 and serotonin 5-HT2A receptors (antagonist); 5-HT1A shown

**Used for**
Schizophrenia in adults · Bipolar I disorder

**Key effects**
Oral numbness · Sleepiness and dizziness

**Monitor**
Weight · Blood pressure lying and standing

**ATC**
N05AH05

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 (antagonist); 5-HT1A shown**Asenapine

ⓘ No asenapine-bound D2 or 5-HT2A structure is available. The figure shows asenapine bound to the human serotonin 5-HT1A receptor with its G protein, another receptor in its broad binding profile.

**Target in 3D:** Dopamine D2 and serotonin 5-HT2A receptors (antagonist); 5-HT1A shown. PDB structure 9DYF (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/9DYF) · Drag to rotate · pinch to zoom

Asenapine is an atypical antipsychotic whose effect is thought to come from combined antagonism at dopamine D2 and serotonin 5-HT2A receptors. It is given under the tongue because, when swallowed, almost all of it is destroyed by first-pass metabolism; under the tongue it is absorbed in minutes but also numbs the mouth.

- Asenapine blocks D2 and 5-HT2A receptors
- Less dopamine signal: less psychosis and mania
- Sublingual route avoids first-pass loss
- Common effects: mouth numbness, sleepiness, akathisia

## Indications

- Schizophrenia in adults [Schizophrenia →](https://durgical.com/en/conditions/schizophrenia/)
- Bipolar I disorder: manic or mixed episodes (also in adolescents), added to lithium or valproate, and maintenance [Bipolar disorder →](https://durgical.com/en/conditions/bipolar-disorder/)

## Adverse effects

### Common

- Oral numbness (hypoaesthesia) and taste change
- Sleepiness and dizziness
- Akathisia and other extrapyramidal effects
- Increased appetite and weight gain

### Serious (rare, important)

- Higher mortality in older people with dementia-related psychosis (boxed warning)
- Severe hypersensitivity: anaphylaxis, angioedema
- Neuroleptic malignant syndrome; tardive dyskinesia
- QT prolongation; orthostatic hypotension
- Hyperglycaemia and dyslipidaemia; low white cell count; seizures

## Contraindications

- Severe hepatic impairment (Child-Pugh C)
- Hypersensitivity to asenapine, including previous anaphylaxis or angioedema

## Key interactions

**Paroxetine**
Asenapine inhibits CYP2D6 and raises paroxetine levels; the paroxetine amount is reduced

**Strong CYP1A2 inhibitors (fluvoxamine)**
Higher asenapine exposure; used with caution

**Antihypertensives**
Added hypotension

**Other QT-prolonging drugs**
Additive QT prolongation

## What is monitored

- Weight, glucose and lipids
- Blood pressure lying and standing
- ECG if QT risk factors
- Abnormal movements

## Administration and safety

- The tablet is placed under the tongue and left to dissolve; it is not split, crushed, chewed or swallowed
- No eating or drinking for 10 minutes afterwards

## Pregnancy and breastfeeding

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

## Nursing care

- Teaches the sublingual technique and checks it is not swallowed
- Warns that the mouth may feel numb and watches for swelling of the tongue or throat, wheezing or rash
- Records weight, glucose and lipids at baseline and during treatment
- Watches for dizziness on standing and sleepiness

## Pharmacokinetics

**Absorption**
Sublingual bioavailability about 35%; below 2% if swallowed. A skin patch form also exists

**Metabolism**
Glucuronidation (UGT1A4) and oxidation, mainly by CYP1A2

**Half-life**
About 24 hours

## Memory aid

«ASENAPINE goes UNDER, not DOWN»: under the tongue it works; swallowed, it is lost. Expect a numb mouth.

## Test yourself

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

## Why is asenapine given sublingually?

Swallowed, its bioavailability is below 2% because of first-pass metabolism; sublingually it is about 35%.

## Which local side effect is typical of asenapine?

Oral hypoaesthesia (numbness of the mouth).

## Which degree of liver disease contraindicates asenapine?

Severe hepatic impairment (Child-Pugh C).

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

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

## Connections

## Related drugs 2

- [Olanzapine](https://durgical.com/en/pharmacology/olanzapine/)
- [Risperidone](https://durgical.com/en/pharmacology/risperidone/)

## Related conditions 2

- [Schizophrenia](https://durgical.com/en/conditions/schizophrenia/)
- [Bipolar disorder](https://durgical.com/en/conditions/bipolar-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: [DailyMed - ASENAPINE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cf587c48-9cd2-4dc5-b0e9-21783c5633a6) (DailyMed (U.S. National Library of Medicine), 2026); [Asenapine: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a610015.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N05AH05) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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