Details
Stereochemistry | ACHIRAL |
Molecular Formula | C28H29F2N3O |
Molecular Weight | 461.5462 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
FC1=CC=C(C=C1)C(CCCN2CCC(CC2)N3C(=O)NC4=CC=CC=C34)C5=CC=C(F)C=C5
InChI
InChIKey=YVUQSNJEYSNKRX-UHFFFAOYSA-N
InChI=1S/C28H29F2N3O/c29-22-11-7-20(8-12-22)25(21-9-13-23(30)14-10-21)4-3-17-32-18-15-24(16-19-32)33-27-6-2-1-5-26(27)31-28(33)34/h1-2,5-14,24-25H,3-4,15-19H2,(H,31,34)
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/10762666
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/10762666
Pimozide (Orap) is a diphenylbutylpiperidine that is effective as an antipsychotic agent and as an alternative to haloperidol for the suppression of vocal and motor tics in patients with Tourette syndrome. It is not intended as a treatment of first choice nor is it intended for the treatment of tics that are merely annoying or cosmetically troublesome. It should be reserved for use in Tourette’s Disorder patients whose development and/or daily life function is severely compromised by the presence of motor and phonic tics. Evidence supporting approval of pimozide for use in Tourette’s Disorder was obtained in two controlled clinical investigations, which enrolled patients between the ages of 8 and 53 years. Most subjects in the two trials were 12 or older. 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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11511086 |
18.0 nM [IC50] | ||
Target ID: CHEMBL2096905 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8301582 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | ORAP Approved UseINDICATIONS & USAGE Pimozide Tablets, USP is indicated for the suppression of motor and phonic tics in patients with Tourette’s Disorder who have failed to respond satisfactorily to standard treatment. Pimozide Tablets, USP is not intended as a treatment of first choice nor is it intended for the treatment of tics that are merely annoying or cosmetically troublesome. Pimozide Tablets, USP should be reserved for use in Tourette’s Disorder patients whose development and/or daily life function is severely compromised by the presence of motor and phonic tics. Evidence supporting approval of Pimozide Tablets, USP for use in Tourette’s Disorder was obtained in two controlled clinical investigations which enrolled patients between the ages of 8 and 53 years. Most subjects in the two trials were 12 or older. Launch Date1984 |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.261 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3480904 |
2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered: |
PIMOZIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
0.347 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3480904 |
2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered: |
PIMOZIDE plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
109 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3480904 |
2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered: |
PIMOZIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
57 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3480904 |
2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered: |
PIMOZIDE plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
6 mg 1 times / day single, oral Overdose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: |
healthy, 1.5 n = 1 Health Status: healthy Age Group: 1.5 Sex: F Population Size: 1 Sources: |
Other AEs: Tremor, Tongue thrust... Other AEs: Tremor Sources: Tongue thrust Drooling Drowsiness Slow response to stimuli Blood pressure decreased |
100 mg 1 times / day single, oral Overdose Dose: 100 mg, 1 times / day Route: oral Route: single Dose: 100 mg, 1 times / day Sources: |
healthy, 17 n = 1 Health Status: healthy Age Group: 17 Sex: F Population Size: 1 Sources: |
Other AEs: Tremor... |
0.2 mg/kg 1 times / day multiple, oral Recommended Dose: 0.2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.2 mg/kg, 1 times / day Sources: |
unhealthy, 2-13 n = 20 Health Status: unhealthy Condition: Tourette's syndrome Age Group: 2-13 Sex: M+F Population Size: 20 Sources: |
Disc. AE: Akathisia, Akinesia... AEs leading to discontinuation/dose reduction: Akathisia Sources: Akinesia |
800 mg 1 times / day single, oral Overdose Dose: 800 mg, 1 times / day Route: oral Route: single Dose: 800 mg, 1 times / day Sources: |
healthy, 53 n = 1 Health Status: healthy Age Group: 53 Sex: F Population Size: 1 Sources: |
Other AEs: Torsades de pointes, Electrocardiogram QTc interval prolonged... Other AEs: Torsades de pointes Sources: Electrocardiogram QTc interval prolonged |
21 mg 1 times / day multiple, oral Highest studied dose Dose: 21 mg, 1 times / day Route: oral Route: multiple Dose: 21 mg, 1 times / day Sources: |
unhealthy, adult n = 51 Health Status: unhealthy Condition: chronic schizophrenia Age Group: adult Sex: M+F Population Size: 51 Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Blood pressure decreased | 6 mg 1 times / day single, oral Overdose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: |
healthy, 1.5 n = 1 Health Status: healthy Age Group: 1.5 Sex: F Population Size: 1 Sources: |
|
Drooling | 6 mg 1 times / day single, oral Overdose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: |
healthy, 1.5 n = 1 Health Status: healthy Age Group: 1.5 Sex: F Population Size: 1 Sources: |
|
Drowsiness | 6 mg 1 times / day single, oral Overdose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: |
healthy, 1.5 n = 1 Health Status: healthy Age Group: 1.5 Sex: F Population Size: 1 Sources: |
|
Slow response to stimuli | 6 mg 1 times / day single, oral Overdose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: |
healthy, 1.5 n = 1 Health Status: healthy Age Group: 1.5 Sex: F Population Size: 1 Sources: |
|
Tongue thrust | 6 mg 1 times / day single, oral Overdose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: |
healthy, 1.5 n = 1 Health Status: healthy Age Group: 1.5 Sex: F Population Size: 1 Sources: |
|
Tremor | 6 mg 1 times / day single, oral Overdose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: |
healthy, 1.5 n = 1 Health Status: healthy Age Group: 1.5 Sex: F Population Size: 1 Sources: |
|
Tremor | 100 mg 1 times / day single, oral Overdose Dose: 100 mg, 1 times / day Route: oral Route: single Dose: 100 mg, 1 times / day Sources: |
healthy, 17 n = 1 Health Status: healthy Age Group: 17 Sex: F Population Size: 1 Sources: |
|
Akathisia | Disc. AE | 0.2 mg/kg 1 times / day multiple, oral Recommended Dose: 0.2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.2 mg/kg, 1 times / day Sources: |
unhealthy, 2-13 n = 20 Health Status: unhealthy Condition: Tourette's syndrome Age Group: 2-13 Sex: M+F Population Size: 20 Sources: |
Akinesia | Disc. AE | 0.2 mg/kg 1 times / day multiple, oral Recommended Dose: 0.2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.2 mg/kg, 1 times / day Sources: |
unhealthy, 2-13 n = 20 Health Status: unhealthy Condition: Tourette's syndrome Age Group: 2-13 Sex: M+F Population Size: 20 Sources: |
Electrocardiogram QTc interval prolonged | 800 mg 1 times / day single, oral Overdose Dose: 800 mg, 1 times / day Route: oral Route: single Dose: 800 mg, 1 times / day Sources: |
healthy, 53 n = 1 Health Status: healthy Age Group: 53 Sex: F Population Size: 1 Sources: |
|
Torsades de pointes | 800 mg 1 times / day single, oral Overdose Dose: 800 mg, 1 times / day Route: oral Route: single Dose: 800 mg, 1 times / day Sources: |
healthy, 53 n = 1 Health Status: healthy Age Group: 53 Sex: F Population Size: 1 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | ||||
yes | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 9, 15 |
major | |||
Page: 9.0 |
minor | |||
Page: 9, 10, 15 |
minor | yes (co-administration study) Comment: coadministration with paroxetine resulted in a 151% increase in pimozide AUC and 62% increase in pimozide Cmax. Page: 9, 10, 15 |
||
yes |
PubMed
Title | Date | PubMed |
---|---|---|
The effect of 5-hydroxytrytamine synthesis inhibitors on neuroleptic-induced catalepsy in rats. | 1975 |
|
Pharmacological options for the treatment of Tourette's disorder. | 2001 |
|
Delusions of parasitosis. A dermatologist's guide to diagnosis and treatment. | 2001 |
|
Comparative safety of the different macrolides. | 2001 |
|
Psychogenic excoriation. Clinical features, proposed diagnostic criteria, epidemiology and approaches to treatment. | 2001 |
|
Tourette syndrome: clinical characteristics and current management strategies. | 2001 |
|
Low-voltage-activated calcium channels are not involved in capacitation and biological response to progesterone in human sperm. | 2001 Dec |
|
Agonist, antagonist, and inverse agonist properties of antipsychotics at human recombinant 5-HT(1A) receptors expressed in HeLa cells. | 2001 Dec 14 |
|
Neurotropic and psychotropic drugs in dermatology. | 2001 Jan |
|
Pimozide (Orap) prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current in native cardiac myocytes. | 2001 Jul |
|
The role of dopamine in the timing of Pavlovian conditioned keypecking in ring doves. | 2001 Jul-Aug |
|
Ophthalmic manifestations of Gilles de la Tourette syndrome. | 2001 Jul-Sep |
|
Inhibition of T-cell invasion across cultured fibroblast monolayers by phenothiazine-related calmodulin inhibitors: impairment of lymphocyte motility by trifluoperazine and chlorpromazine, and alteration of the monolayer by pimozide. | 2001 May 15 |
|
Evidence for the involvement of dopamine D(1) and D(2) receptors in mediating the decrease of food intake during repeated treatment with amphetamine. | 2001 Nov-Dec |
|
Effects of psychotropic drugs on seizure threshold. | 2002 |
|
The effects of naltrexone, an opioid receptor antagonist, on plasma LH levels in common carp (Cyprinus carpio L.). | 2002 Apr |
|
In vitro inhibition of pimozide N-dealkylation by selective serotonin reuptake inhibitors and azithromycin. | 2002 Apr |
|
Delusional parasitosis in leprosy. | 2002 Apr-Jun |
|
Neuroleptic withdrawal versus serotonergic syndrome in an 8-year-old child. | 2002 Fall |
|
Atypical antipsychotics: mechanism of action. | 2002 Feb |
|
Differential inhibition of T-type calcium channels by neuroleptics. | 2002 Jan 15 |
|
Seasonal short-term effects of naltrexone on LH secretion in male carp (Cyprinus carpio L.). | 2002 Mar |
|
Drug interactions of clinical significance for the dermatologist: recognition and avoidance. | 2003 |
|
P300 changes in major depressive disorders with and without psychotic features. | 2003 Feb |
|
A boy with a disabling cough. | 2003 Feb 22 |
|
Antipsychotic augmentation for treatment resistant obsessive-compulsive disorder: what if antipsychotic is discontinued? | 2003 Jan |
|
Inhibitory effects of pimozide on cloned and native voltage-gated potassium channels. | 2003 Jul 4 |
|
Cannabinoid pharmacological properties common to other centrally acting drugs. | 2003 Jun 27 |
|
H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. | 2003 Mar |
|
8-[3H]-hydroxy-2-(di-n-propylamino)tetralin binding sites in blood lymphocytes of rats and the modulation by mitogens and immobilization. | 2003 May |
|
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia. | 2003 Nov 17 |
|
Tic reduction with risperidone versus pimozide in a randomized, double-blind, crossover trial. | 2004 Feb |
Patents
Sample Use Guides
Children:
Treatment should be initiated at a dose of 0.05 mg/kg preferably taken once at bedtime. The dose may be increased every third day to a maximum of 0.2 mg/kg not to exceed 10 mg/day.
Adults:
treatment should be initiated with a dose of 1 to 2 mg a day in divided doses. The dose may be increased thereafter every other day. Most patients are maintained at less than 0.2 mg/kg/day, or 10 mg/day, whichever is less. Doses greater than 0.2 mg/kg/day or 10 mg/day are not recommended. At doses above 4 mg/day, CYP 2D6 genotyping should be performed. In poor CYP 2D6 metabolizers, doses should not exceed 4 mg/day, and doses should not be increased earlier than 14 days.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12824052
Pimozide (PMZD) (10 uM) had minimal effect on Kv1.4, and had no effect on the M-current candidates, KCNQ2 and KCNQ3 when co-expressed in Xenopus oocytes. In hippocampal neurons, PMZD inhibited the delayed rectifiers by approximately 60%, and A-type currents were insensitive to PMZD. The results suggest that PMZD inhibits certain neuronal Kv channels in heterologous expression systems and in hippocampal neurons. PMZD was less effective on A-type currents, presumably because its ability to block requires a prolonged opening of the K channels.
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C29710
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LIVERTOX |
NBK548846
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WHO-ATC |
N05AG02
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NDF-RT |
N0000180182
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WHO-VATC |
QN05AG02
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m8816
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Pimozide
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C47672
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1HIZ4DL86F
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2172
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8331
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DB01100
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16362
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DTXSID8023474
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SUB09847MIG
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218-171-7
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1539508
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PIMOZIDE
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100000081975
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2062-78-4
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1HIZ4DL86F
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2330
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CHEMBL1423
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)