PMID: 8584620Oct 1, 1995Paper

Comparison of cytotoxicity of a quaternary pyridinium metabolite of haloperidol (HP+) with neurotoxin N-methyl-4-phenylpyridinium (MPP+) towards cultured dopaminergic neuroblastoma cells

Psychopharmacology
J FangP H Yu

Abstract

Haloperidol has recently been found to be metabolized to its pyridinium ion (HP+). This conversion of haloperidol to HP+ appears to be similar to the activation of the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to N-methyl-4-phenyl pyridinium ion (MPP+). MPP+ is responsible for the damage of striatal dopaminergic neurons induced by MPTP in humans and animals. It seemed sensible to investigate whether or not HP+ might be toxic towards dopaminergic neurons and perhaps associated with some of the residual moto-function side effects of haloperidol. We therefore investigated the neurotoxicity of HP+ toward cultured human dopamine neuroblastoma cells (SH-SY5Y) and compared it with that of MPP+. HP+ reduced the viability as measured by MTT and [3H]thymidine incorporation methods in SH-SY5Y cells. Cell membrane integrity is reduced by the treatment of HP+ as measured by intracellular LDH levels. The toxicity was concentration and time dependent. Interestingly, HP+ appeared to be more toxic than MPP+ towards the SH-SY5Y cells in early phase in cultures. The toxicity of MPP+ appear to be progressive and subsequently become more than HP+ with prolonged cultivation. In contrary to MPP+, the toxic effect of ...Continue Reading

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Citations

Oct 26, 2000·Journal of Chromatography. B, Biomedical Sciences and Applications·K IgarashiN Castagnoli
Dec 9, 1998·Drug Metabolism Reviews·E UsukiN Castagnoli
Jan 17, 2012·Bioorganic & Medicinal Chemistry·Kwakye PeprahSeth Y Ablordeppey
Jul 18, 2008·Journal of Neurochemistry·Peethambaran ArunAryan M A Namboodiri
Nov 7, 2015·Journal of Applied Toxicology : JAT·Andreas Svennebring
Feb 13, 2001·British Journal of Clinical Pharmacology·J G ShinD A Flockhart
Apr 21, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ho-Jin KangJae-Gook Shin
Jun 5, 2012·Neuropharmacology·Sadayuki HashiokaPatrick L McGeer
Sep 26, 1997·Chemical Research in Toxicology·N CastagnoliK P Castagnoli
May 14, 2008·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·C L Dalla CorteJ B T Rocha

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