| Two pyridinium metabolites of haloperidol are present in the brain of patients at post-mortem. | |
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MedLine Citation:
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PMID: 9042387 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have shown in patients taking the antipsychotic drug haloperidol (HP) that two pyridinium metabolites (HPP+ and RHPP+) are present in blood and urine in nM concentrations. These metabolites are structurally analogous to MPP+, the neurotoxic metabolite of the well-known parkinsonian-producing protoxin, MPTP. In this study we measured the concentrations of HPP+ and RHPP+ in seven regions of the brain (putamen, substantia nigra, globus pallidus, caudate, hippocampus, cerebellum and occipital cortex) obtained at post-mortem from three patients who were taking HP before death. Blood, urine, and bile from one patient were analysed as well. HPP+ was present in all regions (except for substantia nigra in one patient and globus pallidus in another); the amount/g ranged from 1.6-8.3 pMol but there was no preferential sequestration of the metabolite in dopaminergic regions. Similarly, RHPP+ was present relatively uniformly in all regions; the amount/g ranged from 1.1-7.6 pMol. The concentrations of HPP+ and RHPP+ in one patient were 24 and 13 nM in blood, 660 and 230 nM in urine, and 13.0 and 1.4 microM in bile, respectively. The presence of these pyridinums in brain adds another important piece of information to the case that, at least for HP, metabolite-induced neurotoxicity could contribute to the extrapyramidal side-effects in patients receiving long-term therapy. |
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Authors:
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D W Eyles; K M Avent; T J Stedman; S M Pond |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Life sciences Volume: 60 ISSN: 0024-3205 ISO Abbreviation: Life Sci. Publication Date: 1997 |
Date Detail:
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Created Date: 1997-03-25 Completed Date: 1997-03-25 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0375521 Medline TA: Life Sci Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 529-34 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antipsychotic Agents
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metabolism* Autopsy Bile / metabolism Brain / metabolism* Chromatography, High Pressure Liquid Haloperidol / analogs & derivatives*, blood, metabolism*, urine Humans Pyridinium Compounds / blood, metabolism*, urine Reference Standards Tissue Distribution |
| Chemical | |
Reg. No./Substance:
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0/4-(4-chlorophenyl)-1-(4-(4-fluoro-phenyl))-4-hydroxybutylpyridinium; 0/Antipsychotic Agents; 0/Pyridinium Compounds; 125785-69-5/N-(4'-fluorobutyrophenone)-4-(4-chlorophenyl)pyridinium; 52-86-8/Haloperidol |
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