Fluphenazine
First-generation antipsychotics
First-generation antipsychotics
A high-potency phenothiazine antipsychotic. Its long-acting decanoate injection is a WHO essential medicine for schizophrenia.
Quick facts
- Group
- First-generation antipsychotics
- Target
- Dopamine D2 receptor
- Used for
- Schizophrenia · Long-term maintenance
- Key effects
- Acute dystonia · Drowsiness · Dizziness on standing
- Monitor
- Extrapyramidal signs · Full blood count · Weight
- ATC
- N05AB02
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows haloperidol, another high-potency antipsychotic, in the human D2 receptor; fluphenazine blocks the same site (no fluphenazine-bound D2 structure is available).
Fluphenazine is a trifluoromethyl (piperazine) phenothiazine that blocks dopamine D2 receptors strongly. Blocking mesolimbic D2 receptors reduces hallucinations, delusions and hostility. Because it binds D2 tightly and has little anticholinergic action, nigrostriatal block causes many extrapyramidal effects, and pituitary block raises prolactin. Sedation and blood-pressure effects are smaller than with low-potency phenothiazines such as chlorpromazine. The decanoate ester in oil is released slowly from the muscle, so one injection lasts for weeks.
- Strong block of D2 receptors
- Mesolimbic block: fewer positive symptoms
- Nigrostriatal block: extrapyramidal effects
- Decanoate ester releases slowly from muscle for weeks
Indications
- Schizophrenia and other psychotic disorders Schizophrenia →
- Long-term maintenance by injection when daily tablets are not reliable Schizophrenia →
Adverse effects
Common
- Acute dystonia, akathisia and parkinsonism
- Drowsiness, dry mouth
- Breast enlargement or discharge, missed periods, sexual problems
- Dizziness on standing; sensitivity to sun and heat
Contraindications
- Suspected subcortical brain damage
- Coma, severe CNS depression or large doses of hypnotics
- Blood dyscrasias or liver damage
- Children under 12 (decanoate); hypersensitivity to phenothiazines
Key interactions
- Alcohol, hypnotics and other CNS depressants
- Additive sedation.
- Anticholinergic drugs
- Added anticholinergic effects, including heat intolerance.
- Tobacco smoking
- May reduce its effect.
What is monitored
- Extrapyramidal signs and abnormal involuntary movements
- Full blood count, especially with fever or sore throat
- Weight, blood pressure and liver tests
- Fever with rigidity (neuroleptic malignant syndrome)
Administration and safety
- Decanoate: deep intramuscular (or subcutaneous) injection with a dry syringe and needle; moisture clouds the oily solution.
- Oral concentrate is diluted in a suitable drink just before use.
- Injection days are scheduled and missed doses are followed up.
Pregnancy and breastfeeding
Newborns exposed in the third trimester may have extrapyramidal or withdrawal symptoms; use weighs benefit and risk.
Nursing care
- Before: check for movement disorders, liver disease and blood disorders.
- During: watch for dystonia (neck, jaw, eyes) in the first days; anticholinergic rescue is kept at hand.
- Ask about restlessness and stiffness; screen regularly for tardive dyskinesia.
- Teach sun protection, to rise slowly and to avoid overheating.
Pharmacokinetics
- Absorption
- Oral tablets and liquids; decanoate injection is absorbed slowly from the injection site.
- Onset and duration
- The decanoate keeps working for weeks after each injection.
Test yourself
Think of the answer, then tap the question to see it.
Why does fluphenazine cause more extrapyramidal effects than chlorpromazine?
It is a high-potency D2 blocker with little anticholinergic action.
What makes fluphenazine decanoate last for weeks?
The ester in oil is released slowly from the muscle and then hydrolysed to fluphenazine.
What practical point matters when drawing up fluphenazine decanoate?
Use a dry syringe and needle; water clouds the solution.
Connections
← Back to the class: First-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: Fluphenazine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); FLUPHENAZINE DECANOATE injection, solution (DailyMed (U.S. National Library of Medicine), 2026); Haloperidol bound D2 dopamine receptor structure inspired discovery of subtype selective ligands (RCSB Protein Data Bank, 2020); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.