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| Clinical data | |
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| Trade names | Orap |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a686018 |
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| Routes of administration | Oral |
| Drug class | Typical antipsychotic |
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| Pharmacokinetic data | |
| Bioavailability | 40-50% |
| Metabolism | CYP3A4,CYP1A2 andCYP2D6 |
| Eliminationhalf-life | 55 hours (adults), 66 hours (children) |
| Excretion | Urine |
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| ECHA InfoCard | 100.016.520 |
| Chemical and physical data | |
| Formula | C28H29F2N3O |
| Molar mass | 461.557 g·mol−1 |
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Pimozide (sold under the brand nameOrap) is a neurolepticdrug of thediphenylbutylpiperidine class. It was discovered atJanssen Pharmaceutica in 1963. It has a high potency compared tochlorpromazine (ratio 50-70:1). On a weight basis it is even more potent thanhaloperidol. It also has special indication forTourette syndrome and resistanttics.
Pimozide is used for Tourette syndrome,[2] and resistanttics (Europe, United States, and Canada) and in Europe forschizophrenia, chronicpsychosis,delusional disorder, andparanoid personality disorder.[3]
A 2013systematic review compared pimozide with other antipsychotics for schizophrenia or related psychoses: Pimozide versus any other antipsychotic[4]
In one case a series of 33 patients with delusional parasitosis (median age, 60 years), pimozide was prescribed for 24 patients, 18 of whom took the drug. The dose ranged from 1 to 5 mg daily. No information regarding initial dosing was specified, although the dose was continued for 6 weeks prior to tapering. Of those patients receiving pimozide, 61% (11/18) experienced improvement in or full remission of symptoms. The use of pimozide for the treatment of delusional parasitosis is based primarily on data from case series/reports that demonstrate some efficacy in the majority of patients. Currently,atypical antipsychotics such asolanzapine orrisperidone are used as first line treatment. However, patients who experience negative side-effects with the first line medications are typically given pimozide.[5][6]
It is contraindicated in individuals with either acquired, congenital or a family history of QT interval prolongation.[7] Its use is advised against in individuals with people with either a personal or a family history of arrhythmias ortorsades de pointes.[7] Likewise its use is also advised against in individuals with uncorrectedhypokalaemia andhypomagnesaemia or clinical significant cardiac disorders (e.g. a recentmyocardial infarction orbradycardia.[7] It is also contraindicated in individuals being cotreated withselective serotonin reuptake inhibitors (SSRI) or in those with a known hypersensitivity to pimozide or other diphenylbutyl-piperidine derivatives.[7] Likewise its use is contraindicated in individuals receiving treatment withCYP3A4,CYP1A2, orCYP2D6 inhibitors.[7]
Very common (>10% frequency) side effects include:[8][7][9][10]
Pimozide overdose presents with severeextrapyramidal symptoms,hypotension,sedation, QT interval prolongation and ventricular arrhythmias includingtorsades de pointes.[7] Gastric lavage, establishment of a patent airway and, if necessary, mechanically assisted respiration is the recommended treatment for pimozide overdose.[7] Cardiac monitoring should be continued for at least 4 days due to the long half-life of pimozide.[7]
Pimozide acts as anantagonist of theD2,D3, andD4 receptors and the5-HT7 receptor. It is also ahERGblocker.
Similarly to other typical antipsychotics pimozide has a high affinity for thedopamine D2 receptor and this likely results in its sexual (due toprolactin hypersecretion) and extrapyramidal side effects as well as its therapeutic efficacy against the positive symptoms ofschizophrenia.[11]
| Protein | Ki (nM)[12] | Notes |
|---|---|---|
| 5-HT1A | 650 | |
| 5-HT2A | 48.4 | This receptor is believed to be responsible for the atypicality of other antipsychotics likeclozapine,olanzapine andquetiapine. Pimozide's affinity towards this receptor is low compared to its affinity for the D2 receptor and hence this receptor unlikely contributes to its effects to any meaningful extent. |
| 5-HT2C | 2,112 | |
| 5-HT6 | 71 | |
| 5-HT7 | 0.5 | Relatively high affinity for this receptor may explain its supposed antidepressant-like effects in animal models of depression.[13] |
| α1A | 197.7 | Low affinity towards this receptor may explain why pimozide has a lower liability for producing orthostatic hypotension.[11] |
| α2A | 1,593 | |
| α2B | 821 | |
| α2C | 376.5 | |
| M3 | 1,955 | This receptor is believed to be responsible for the interference with glucosehomeostasis seen with some of theatypical antipsychotics such asclozapine andolanzapine.[14] Pimozide's low affinity for this receptor likely contributes to the comparatively mild effects on glucose homeostasis. |
| D1 | >10,000 | |
| D2 | 0.33 | Likely the receptor responsible for the therapeutic effects against the positive symptoms of schizophrenia of antipsychotics like pimozide as well as the prolactin-elevating and extrapyramidal side effect-generating effects of typical antipsychotics like pimozide.[14] |
| D3 | 0.25 | |
| D4 | 1.8 | |
| hERG | 18 | May be responsible for pimozide's high liability for prolonging the QT interval.[14] |
| H1 | 692 | Likely responsible for why pimozide tends to produce so little sedation.[14] |
| σ | 508 |
| Pharmacokinetic parameter | Value |
|---|---|
| Time to peak plasma concentration (Tmax) | 6-8 hr |
| Peak plasma concentration (Cmax) | 4-19 ng/mL |
| Elimination half-life (t1/2) | 55 hours (adults), 66 hours (children) |
| Metabolising enzymes | CYP3A4,CYP1A2 andCYP2D6 |
| Excretion pathways | Urine |
In 1985 pimozide was approved by the FDA for marketing as anorphan drug for the treatment of Tourette's syndrome.[2]
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