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.
Quick facts
- Group
- 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.
Mechanism of action
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.
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 →
- Bipolar I disorder: manic or mixed episodes (also in adolescents), added to lithium or valproate, and maintenance Bipolar disorder →
Adverse effects
Common
- Oral numbness (hypoaesthesia) and taste change
- Sleepiness and dizziness
- Akathisia and other extrapyramidal effects
- Increased appetite and weight gain
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
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).
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: DailyMed - ASENAPINE tablet (DailyMed (U.S. National Library of Medicine), 2026); Asenapine: 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.