Pimozide
First-generation antipsychotics
First-generation antipsychotics
A potent D2-blocking antipsychotic kept for severe Tourette tics. It lengthens the QT interval, so ECGs and CYP3A4/2D6 interactions matter.
Quick facts
- Group
- First-generation antipsychotics
- Target
- Dopamine D2 receptor (antagonist); hERG potassium channel shown
- Used for
- Suppression of severe motor
- Key effects
- Weakness · Extrapyramidal effects · Raised prolactin
- Monitor
- ECG at baseline and periodically · Abnormal movements
- ATC
- N05AG02
No doses: the clinician sets them by the current guideline.
Mechanism of action
No pimozide-bound D2 structure exists. The figure shows pimozide blocking the pore of the human hERG potassium channel, the off-target action behind its QT prolongation.
Pimozide is a diphenylbutylpiperidine that blocks dopamine D2 receptors, and this is thought to suppress motor and vocal tics. It also blocks the cardiac hERG potassium channel, which slows repolarisation and lengthens the QT interval. Because it is cleared mainly by CYP3A4 (and partly by CYP2D6), any drug that blocks these enzymes raises its level and the risk of ventricular arrhythmia.
- Pimozide blocks D2 receptors
- Less dopamine signalling: fewer motor and vocal tics
- It also blocks the cardiac hERG channel
- Longer QT: risk of torsades, worse with CYP3A4 inhibitors
Indications
- Suppression of severe motor and phonic tics in Tourette disorder that has not responded to standard treatment Tourette syndrome and tic disorders →
Adverse effects
Common
- Weakness, dizziness and unsteadiness
- Extrapyramidal effects: mainly parkinsonism, less often dystonia and akathisia
- Raised prolactin: breast changes, menstrual changes
- Dry mouth, constipation
Contraindications
- Simple tics or tics not due to Tourette disorder
- Congenital long QT, history of arrhythmia, or other QT-prolonging drugs
- Low potassium or low magnesium
- Macrolides, azole antifungals (itraconazole, ketoconazole), HIV protease inhibitors and nefazodone (CYP3A4 inhibitors)
- Paroxetine and other strong CYP2D6 inhibitors; sertraline, citalopram or escitalopram
- Severe CNS depression or coma
Key interactions
- Clarithromycin, erythromycin and other macrolides
- Higher pimozide levels and QT prolongation: sudden deaths reported
- Other QT-prolonging drugs (class Ia and III antiarrhythmics, some antipsychotics and fluoroquinolones)
- Additive QT prolongation
- Grapefruit juice
- May block CYP3A4 and raise pimozide levels
- Stimulants (methylphenidate, amphetamines)
- Can themselves cause tics, which must be ruled out first
What is monitored
- ECG at baseline and periodically, especially while adjusting
- Potassium and magnesium
- CYP2D6 genotype when higher amounts are considered
- Abnormal movements
Administration and safety
- Every new medicine is checked for CYP3A4/CYP2D6 inhibition and QT effect before it is added
- Low potassium (from diuretics, diarrhoea) is corrected before and during treatment
Pregnancy and breastfeeding
Newborns exposed in the third trimester may have extrapyramidal or withdrawal symptoms; it is used only if the benefit clearly outweighs the risk.
Nursing care
- Checks that a baseline ECG and electrolytes are on record before the first dose
- Reports palpitations, fainting or a lengthening QT at once
- Teaches the patient to avoid grapefruit juice and to mention pimozide before any new antibiotic or antifungal
- Watches for stiffness, restlessness, abnormal movements and fever
Pharmacokinetics
- Absorption
- Taken by mouth, with marked first-pass metabolism; peak after several hours
- Metabolism
- Liver, mainly CYP3A4, also CYP1A2 and CYP2D6; levels vary widely between people
- Elimination
- Mainly through the kidneys as metabolites
- Half-life
- Long: about 55 hours in the studied patients
Test yourself
Think of the answer, then tap the question to see it.
For which condition is pimozide reserved?
Severe motor and phonic tics of Tourette disorder that did not respond to standard treatment.
Why is clarithromycin contraindicated with pimozide?
It blocks CYP3A4, raises pimozide levels and adds QT prolongation; sudden deaths have been reported.
Which tests are done before and during pimozide treatment?
An ECG (QT interval) and potassium and magnesium levels.
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: DailyMed - PIMOZIDE tablet (DailyMed (U.S. National Library of Medicine), 2026); Pimozide: 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.