Pimozide

Structural formula
General
Non-proprietary name	Pimozide
other names	1- {1- [4,4-bis (4-fluorophenyl) butyl] -4-piperidyl} -2,3-dihydrobenzimidazol-2-one
Molecular formula	C 28 H 29 F 2 N 3 O
Brief description	white to almost white powder
External identifiers / databases
EC number	218-171-7
ECHA InfoCard	100.016.520
PubChem	16362
DrugBank	DB01100
Wikidata	Q144085
Drug information
ATC code	N05 AG02
Drug class	Antipsychotic
properties
Molar mass	461.55 g · mol -1
Physical state	firmly
Melting point	214-218 ° C
pK s value	8.63
solubility	almost insoluble in water (10 mg l −1 at 25 ° C); soluble in dichloromethane , little in methanol , poor in ethanol ;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302
	P: no P-phrases
Toxicological data	228 mg kg −1 ( LD 50 , mouse , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Pimozide ( trade name Orap ) is a drug from the group of antipsychotics , which is used in the form of tablets in the treatment of chronic psychoses of the schizophrenic type.

Clinical information

Dosis, kind and Time of the Use

Orap is available in strengths of 1 mg and 4 mg. The therapy is started with low doses, which are increased up to the maintenance dose to be determined by the doctor (in adult therapy usually 2 to 12 mg per day).

Contraindications (contraindications)

The drug must not be used in conditions that are accompanied by severe depression of the central nervous system , in certain pre-existing heart diseases and disorders of the electrolyte balance . There was an increased mortality in elderly people with dementia, which is why the drug is not approved for patients with dementia.

Simultaneous use of drugs that inhibit the cytochromes CYP3A4 and CYP2D6 leads to higher active levels and undesirable drug effects, while inducers of these enzymes lead to increased breakdown.

Simultaneous use with serotonin reuptake inhibitors such as sertraline , paroxetine , citalopram or escitalopram is contraindicated due to the serotonergic effect.

Use during pregnancy and breastfeeding

Pimozide should only be used during pregnancy after careful consideration of the risk-benefit ratio, as the potential risk to humans is unknown. Pimozide is excreted in breast milk, so you should not breast-feed during treatment.

Special patient groups (diabetics, kidney patients)

Particular care should be taken when treating patients with endogenous depression , Parkinson's disease , liver disease, or seizures .

Adverse effects (side effects)

The undesirable effects are predominantly psychiatric (insomnia, anxiety) or affect the nervous system (drowsiness, headache).

Cardiac effects such as prolongation of the ECG QT time , torsade de pointes tachycardia , ventricular arrhythmias including ventricular fibrillation, ventricular tachycardia and cardiac arrest have been reported with antipsychotics . There were also unexplained sudden deaths. Specific to pimozide, side effects such as erectile dysfunction , exhaustion, weight gain, nocturia and pollakiuria and overactive sebum glands are common, and hyperhidrosis is very common.

Pharmacological properties

Mechanism of action (pharmacodynamics)

The effect presumably comes about through a postsynaptic occupation of dopamine receptors , which presynaptically stimulate increased dopamine release . This increased dopamine release is apparently stronger than the low level of receptor occupancy, so that the postsynaptic receptors are activated. Pimozide also acts as a FIASMA (functional inhibitor of acid sphingomyelinase ). Pimozide works against hallucinations and delusional ideas without dampening.

toxicology

Acute toxicological effects of pimozide mainly affect the central nervous system and the cardiovascular system .

Chemical information

Pimozid belongs to the group of diphenylbutylpiperidines .

Individual evidence

↑ ^a ^b European Pharmacopoeia Commission (Ed.): European Pharmacopoeia 5th Edition . Basic work (Ph.Eur. 5.0), 2005.
↑ ^a ^b ^c ^d Entry on pimozide in the ChemIDplus database of the United States National Library of Medicine (NLM) .
↑ ^a ^b Data sheet Pimozide from Sigma-Aldrich , accessed on April 20, 2011 ( PDF ).
↑ ^a ^b ^c ^d ^e ^f ^g ^h Specialist information Orap 1 mg, Orap forte 4 mg, Janssen-Cilag, as of April 2007.
↑ ^a ^b ^c Fachinfo Pimozid (ORAP) (PDF; 84 kB) Retrieved on February 16, 2013. ( Page no longer available , search in web archives ) Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. . @1@ 2Template: Dead Link / www.fachinfo.de
↑ Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P: Identification of novel functional inhibitors of acid sphingomyelinase . In: PLoS ONE . 6, No. 8, 2011, p. E23852. doi : 10.1371 / journal.pone.0023852 .

[Ph._Eur._5-1] European Pharmacopoeia Commission (Ed.): European Pharmacopoeia 5th Edition . Basic work (Ph.Eur. 5.0), 2005.

[ChemIDplus-2] Entry on pimozide in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[sigma-3] Data sheet Pimozide from Sigma-Aldrich , accessed on April 20, 2011 ( PDF ).

[fi-4] ↑ ^a ^b ^c ^d ^e ^f ^g ^h Specialist information Orap 1 mg, Orap forte 4 mg, Janssen-Cilag, as of April 2007.

[fi2011-5] Fachinfo Pimozid (ORAP) (PDF; 84 kB) Retrieved on February 16, 2013. ( Page no longer available , search in web archives ) Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. . @1@ 2Template: Dead Link / www.fachinfo.de

[pmid18504571-6] Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P: Identification of novel functional inhibitors of acid sphingomyelinase . In: PLoS ONE . 6, No. 8, 2011, p. E23852. doi : 10.1371 / journal.pone.0023852 .