Pimozide (sold under the brand name Orap) is a neuroleptic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine (ratio 50-70:1). On a weight basis it is even more potent than haloperidol. It also has special indication for Tourette syndrome and resistant tics.

Medical uses

Pimozide is used for Tourette syndrome,

Efficacy

A 2013 systematic review compared pimozide with other antipsychotics for schizophrenia or related psychoses: Pimozide versus any other antipsychotic

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 as olanzapine or risperidone are used as first line treatment. However, patients who experience negative side-effects with the first line medications are typically given pimozide.

Contraindications

It is contraindicated in individuals with either acquired, congenital or a family history of QT interval prolongation.

{| class="wikitable sortable"

|+ <big>Binding profile</big>

! Protein !! K<sub>i</sub> (nM) !! Notes

|-

| 5-HT<sub>1A</sub> || 650 ||

|-

| 5-HT<sub>2A</sub> || 48.4 || This receptor is believed to be responsible for the atypicality of other antipsychotics like clozapine, olanzapine and quetiapine. Pimozide's affinity towards this receptor is low compared to its affinity for the D<sub>2</sub> receptor and hence this receptor unlikely contributes to its effects to any meaningful extent.

|-

| 5-HT<sub>2C</sub> || 2,112 ||

|-

| 5-HT<sub>6</sub> || 71 ||

|-

| 5-HT<sub>7</sub> || 0.5 || Relatively high affinity for this receptor may explain its supposed antidepressant-like effects in animal models of depression.

|-

| α<sub>1A</sub> || 197.7 || Low affinity towards this receptor may explain why pimozide has a lower liability for producing orthostatic hypotension. Pimozide's low affinity for this receptor likely contributes to the comparatively mild effects on glucose homeostasis.

|-

| D<sub>1</sub> || >10,000 ||

|-

| D<sub>2</sub> || 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.

! Pharmacokinetic parameter !! Value

|-

| Time to peak plasma concentration (T<sub>max</sub>) || 6-8 hr

|-

| Peak plasma concentration (C<sub>max</sub>) || 4-19&nbsp;ng/mL

|-

| Elimination half-life (t<sub>1/2</sub>) || 55 hours (adults), 66 hours (children)

|-

| Metabolising enzymes || CYP3A4, CYP1A2 and CYP2D6

|-

| Excretion pathways || Urine

|}

History

In 1985 pimozide was approved by the FDA for marketing as an orphan drug for the treatment of Tourette's syndrome.

See also

  • Amisulpride
  • Pipamperone
  • Fluspirilene
  • Penfluridol

Notes

References