Literature DB >> 1755019

Dehydration is the first step in the bioactivation of haloperidol to its pyridinium metabolite.

J Fang1, J W Gorrod.   

Abstract

Haloperidol was found to have a similar metabolic pathway to that of the neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice microsomal preparations. The 1,2,3,6-tetrahydropyridine derivative of haloperidol was detected in NADPH-fortified metabolic incubation mixtures of haloperidol. Incubation of this dehydrated haloperidol produced the pyridinium metabolite. These metabolites were confirmed by comparison with synthesised compounds using HPLC and HPLC-MS. Dehydration of an alcohol to a double bond represents a novel metabolic pathway. This novel metabolic pathway indicates a MPTP-like mechanism for the Parkinsonism observed with haloperidol in clinical use.

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Year:  1991        PMID： 1755019     DOI： 10.1016/0378-4274(91)90062-b

Source DB:  PubMed          Journal:  Toxicol Lett        ISSN： 0378-4274            Impact factor:   4.372


  10 in total

1.  Involvement of CYP3A4 and CYP2D6 in the metabolism of haloperidol.

Authors:  J Fang; G B Baker; P H Silverstone; R T Coutts
Journal:  Cell Mol Neurobiol       Date:  1997-04       Impact factor: 5.046

Review 2.  Metabolism, pharmacogenetics, and metabolic drug-drug interactions of antipsychotic drugs.

Authors:  J Fang; J W Gorrod
Journal:  Cell Mol Neurobiol       Date:  1999-08       Impact factor: 5.046

3.  Structure-based design of haloperidol analogues as inhibitors of acetyltransferase Eis from Mycobacterium tuberculosis to overcome kanamycin resistance.

Authors:  Ankita Punetha; Keith D Green; Atefeh Garzan; Nishad Thamban Chandrika; Melisa J Willby; Allan H Pang; Caixia Hou; Selina Y L Holbrook; Kyle Krieger; James E Posey; Tanya Parish; Oleg V Tsodikov; Sylvie Garneau-Tsodikova
Journal:  RSC Med Chem       Date:  2021-10-05

4.  Inhibition of monoamine oxidases by haloperidol and its metabolites: pharmacological implications for the chemotherapy of schizophrenia.

Authors:  J Fang; P H Yu; J W Gorrod; A A Boulton
Journal:  Psychopharmacology (Berl)       Date:  1995-03       Impact factor: 4.530

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

Authors:  J Fang; D Zuo; P H Yu
Journal:  Psychopharmacology (Berl)       Date:  1995-10       Impact factor: 4.530

6.  Effect of haloperidol and its metabolites on dopamine and noradrenaline uptake in rat brain slices.

Authors:  J Fang; P H Yu
Journal:  Psychopharmacology (Berl)       Date:  1995-10       Impact factor: 4.530

7.  Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one.

Authors:  Seth Y Ablordeppey; Ramazan Altundas; Barbara Bricker; Xue Y Zhu; Eyunni V K Suresh Kumar; Tanise Jackson; Abdul Khan; Bryan L Roth
Journal:  Bioorg Med Chem       Date:  2008-06-20       Impact factor: 3.641

8.  Metabolic studies on haloperidol and its tetrahydropyridinyl dehydration product (HPTP) in C57BL/6 mouse brain preparations.

Authors:  Etsuko Usuki; Jeffrey R Bloomquist; Ethan Freeborn; Kay Casagnoli; Cornelis J Van Der Schyf; Neal Castagnoli
Journal:  Neurotox Res       Date:  2002-02       Impact factor: 3.911

9.  N-alkylprotoporphyrin formation and hepatic porphyria in dogs after administration of a new antiepileptic drug candidate: mechanism and species specificity.

Authors:  Jean-Marie Nicolas; Hugues Chanteux; Valérie Mancel; Guy-Marie Dubin; Brigitte Gerin; Ludovicus Staelens; Olympe Depelchin; Sophie Kervyn
Journal:  Toxicol Sci       Date:  2014-06-27       Impact factor: 4.849

Review 10.  The metabolism of alicyclic amines to reactive iminium ion intermediates.

Authors:  J W Gorrod; G Aislaitner
Journal:  Eur J Drug Metab Pharmacokinet       Date:  1994 Jul-Sep       Impact factor: 2.441
  10 in total

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