The neurotoxicity of pyridinium metabolites of haloperidol

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The neurotoxicity of pyridinium metabolites of haloperidol

Agnieszka Górska 1 , Michał Marszałł 1 , Anna Sloderbach 2

1. Katedra i Zakład Chemii Leków, Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu
2. Katedra i Zakład Farmakodynamiki i Farmakologii Molekularnej

Published: 2015-10-19
DOI: 10.5604/17322693.1175009
GICID: 01.3001.0009.6585
Available language versions: en pl
Issue: Postepy Hig Med Dosw 2015; 69 : 1169-1175

 

Abstract

Haloperydol is a butyrophenone, typical neuroleptic agent characterized as a high antipsychotics effects in the treatment of schizophrenia and in palliative care to alleviation many syndromes, such as naursea, vomiting and delirium. Clinical problems occurs during and after administration of the drug are side effects, particularly extrapyrramidal symptoms (EPS). The neurotoxicity of haloperydol may be initiated by the cationic metabolites of haloperydol, HPP+, RHPP+, formed by oxidation and reduction pathways. These metabolites are transported by human organic cation transporters (hOCT) to several brain structures for exapmle, in substantia nigra, striatum, caudate nucleus, hippocampus. After reaching the dopaminergic neurons inhibits mitochondrial complex I, evidence for free radical involvement, thus leading to neurodegeneration.

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