Pimozide: profile and news

Other information

Indication
Used for the suppression of motor and phonic tics in patients with Tourette's Disorder who have failed to respond satisfactorily to standard treatment.

Pharmacology
Pimozide is an orally active antipsychotic drug product which shares with other antipsychotics the ability to blockade dopaminergic receptors on neurons in the central nervous system. Although its exact mode of action has not been established, the ability of Pimozide to suppress motor and phonic tics in Tourette's Disorder is thought to be a function of its dopaminergic blocking activity. However, receptor blockade is often accompanied by a series of secondary alterations in central dopamine metabolism and function which may contribute to both Pimozide's therapeutic and untoward effects. In addition, Pimozide, in common with other antipsychotic drugs, has various effects on other central nervous system receptor systems which are not fully characterized.

Mechanism Of Action
Although its exact mode of action has not been established, the ability of Pimozide to suppress motor and phonic tics in Tourette's Disorder is thought to be a function of its dopaminergic blocking activity. Pimozide binds to the dopamine D2 receptor

Drug Category
Antidyskinetics; Antipsychotics; Antipsychotics; ATC:N05AG02

Brand Names/Synonyms
6238; Haldol Decanoate; Halomonth; KD-136; Mcn-Jr 6238; Neoperidole; Opiran; Orap; Pimozide; Pimozide [Usan:Ban:Inn:Jan]; Pimozidum [Inn-Latin]; Primozida [Inn-Spanish]; R 6238

Dosage Forms
TABLET

Absorption
>50% absorption after oral administration, serum peak appears 6-8 hours post ingestion.

Interactions
-->Interactions for Pimozide:

Because ORAP prolongs the QT interval of the electrocardiogram, an additive effect on QT interval would be anticipated if administered with other drugs, such as phenothiazines, tricyclic antidepressants or antiarrhythmic agents, which prolong the QT interval. Accordingly, pimozide should not be given with dofetilide, sotalol, quinidine, other Class Ia and III anti-arrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, sparfloxacin, gatifloxacin, moxifloxacin, halofantrine, mefloquine, pentamidine, arsenic trioxide, levomethadyl acetate, dolasetron mesylate, probucol, tacrolimus, ziprasidone, or other drugs that have demonstrated QT prolongation as one of their pharmacodynamic effects. Also, the use of macrolide antibiotics in patients with prolonged QT intervals has been rarely associated with ventricular arrhythmias. Such concomitant administration should not be undertaken.

Since ORAP is partly metabolized via CYP 3A4, it should not be administered concomitantly with inhibitors of this metabolic system, such as azole antifungal agents and protease inhibitor drugs.

As CYP 1A2 may also contribute to the metabolism of ORAP, prescribers should be aware of the theoretical potential for drug interactions with inhibitors of this enzymatic system

ORAP may be capable of potentiating CNS depressants, including analgesics, sedatives, anxiolytics, and alcohol.

Rare case reports have suggested possible additive effects of pimozide and fluoxetine leading to bradycardia.

Concomitant administration of pimozide and sertraline should be contraindicated.

Interaction with Food

Patients should avoid grapefruit juice because it may inhibit the metabolism of pimozide by CYP 3A4.

Chemical IUPAC Name
1-[1-[4,4-bis(4-fluorophenyl)butyl]-4-piperidyl]-1,3-dihydrobenzoimidazol-2-one

Chemical Formula
C28H29F2N3O

Half Life
55 hours

Drug Type
Approved Drug

# Accession No
APRD00218

CAS Registry Number
2062-78-4