On the metabolism of haloperidol
| العنوان: | On the metabolism of haloperidol |
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| المؤلفون: | J W Gorrod, Jim Fang |
| المصدر: | Xenobiotica. 23:495-508 |
| بيانات النشر: | Informa UK Limited, 1993. |
| سنة النشر: | 1993 |
| مصطلحات موضوعية: | Butyrophenone, Health, Toxicology and Mutagenesis, Metabolite, Guinea Pigs, Pharmacology, Toxicology, Biochemistry, Mass Spectrometry, Mice, chemistry.chemical_compound, Cricetinae, Haloperidol, medicine, Animals, Rats, Wistar, Chromatography, High Pressure Liquid, MPTP, General Medicine, Metabolism, Rats, chemistry, Toxicity, Microsome, Rabbits, Pyridinium, medicine.drug |
| الوصف: | 1. p-Fluorobenzoyl-propionic acid, 4-(4-chlorophenyl)-4-hydroxy-piperidine, and reduced haloperidol were confirmed as metabolites of haloperidol. Their formation was catalysed by hepatic microsomes and was NADPH dependent. 2. The pyridinium metabolite of haloperidol (HP+) was identified. It is proposed that haloperidol first undergoes dehydration to form its 1,2,3,6-tetrahydropyridine analogue (HTP). HTP is then further metabolized to HP+, HTP N-oxide and its N-dealkylated product, 4-chlorophenyl-1,2,3,6-tetrahydropyridine (CPTP). HTPN-oxide was metabolized to CPTP and HTP. All these metabolites were confirmed by comparison with synthesized compounds using h.p.l.c. and h.p.l.c.-mass spectrometry. 3. Three unknown metabolites were present in microsomal metabolic incubations of haloperidol. One of them was tentatively characterized by h.p.l.c.-mass spectrometry as an oxygenated product of haloperidol, another appears to be the 2-pyridine analogue of haloperidol. The third metabolite was shown to be a neutral compound of unknown structure, which was not haloperidol N-oxide nor 4-hydroxy-4'-fluorobutyrophenone. In addition, HTP was metabolized to a further unknown product with a similar u.v. spectrum to that of HTP. 4. The identification of these metabolites led to the hypothesis that the metabolism of haloperidol is similar to that of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and may therefore produce motor neurone toxicity by a similar mechanism. |
| تدمد: | 1366-5928 0049-8254 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::75280a2566d322b0201b62820a84715d https://doi.org/10.3109/00498259309059390 |
| رقم الأكسشن: | edsair.doi.dedup.....75280a2566d322b0201b62820a84715d |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 13665928 00498254 |
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