CYP3A4和CYP2D6参与氟哌啶醇的代谢。
Involvement of CYP3A4 and CYP2D6 in the metabolism of haloperidol.
作者信息
Fang J, Baker G B, Silverstone P H, Coutts R T
机构信息
Department of Psychiatry, University of Alberta, Edmonton, Canada.
出版信息
Cell Mol Neurobiol. 1997 Apr;17(2):227-33. doi: 10.1023/a:1026317929335.
Abstract
- Human cytochrome P450 (CYP) isoenzymes expressed in a human cell line were used to elucidate their involvement in the metabolism of haloperidol (HAL). 2. It was found that CYP3A4 catalyzes the metabolism of HAL to HAL 1,2,3,6-tetrahydropyridine (HTP). HTP is further metabolized to HAL pyridinium (HP+) by both CYP3A4 and CYP2D6. 3. CYP3A4 and CYP2D6 are also responsible for the N-dealkylation of HAL. The N-dealkylation of reduced HAL (RH) was observed, which is catalyzed by CYP3A4. In addition, CYP3A4 also catalyzes the oxidation of RH back to HAL. 4. These results are discussed in terms of the metabolic interactions of HAL with other drugs and how this knowledge may be used to reduce the movement disorders induced by HAL.
摘要
- 利用在人细胞系中表达的人细胞色素P450（CYP）同工酶来阐明它们在氟哌啶醇（HAL）代谢中的作用。2. 发现CYP3A4催化HAL代谢为HAL 1,2,3,6-四氢吡啶（HTP）。HTP通过CYP3A4和CYP2D6进一步代谢为氟哌啶醇吡啶鎓（HP+）。3. CYP3A4和CYP2D6也负责HAL的N-去烷基化。观察到还原型HAL（RH）的N-去烷基化，它由CYP3A4催化。此外，CYP3A4还催化RH氧化回HAL。4. 根据HAL与其他药物的代谢相互作用以及如何利用这些知识减少HAL引起的运动障碍来讨论这些结果。
相似文献
1
Involvement of CYP3A4 and CYP2D6 in the metabolism of haloperidol.CYP3A4和CYP2D6参与氟哌啶醇的代谢。
Cell Mol Neurobiol. 1997 Apr;17(2):227-33. doi: 10.1023/a:1026317929335.
2
In vitro study on the involvement of CYP1A2, CYP2D6 and CYP3A4 in the metabolism of haloperidol and reduced haloperidol.CYP1A2、CYP2D6和CYP3A4参与氟哌啶醇和还原型氟哌啶醇代谢的体外研究。
Eur J Clin Pharmacol. 1999 Oct;55(8):599-604. doi: 10.1007/s002280050679.
3
In vitro characterization of the metabolism of haloperidol using recombinant cytochrome p450 enzymes and human liver microsomes.利用重组细胞色素P450酶和人肝微粒体对氟哌啶醇代谢进行的体外特性研究。
Drug Metab Dispos. 2001 Dec;29(12):1638-43.
4
Involvement of human cytochrome P450 3A4 in reduced haloperidol oxidation.人细胞色素P450 3A4参与氟哌啶醇氧化还原反应。
Eur J Clin Pharmacol. 1998 May;54(3):253-9. doi: 10.1007/s002280050455.
5
Involvement of CYP3A4 in the metabolism of bromperidol in vitro.
Pharmacol Toxicol. 2000 Mar;86(3):145-8. doi: 10.1034/j.1600-0773.2000.d01-27.x.
6
In-vitro characterization of the cytochrome P450 isoenzymes involved in the back oxidation and N-dealkylation of reduced haloperidol.参与还原氟哌啶醇后氧化和N-脱烷基反应的细胞色素P450同工酶的体外特性研究。
Pharmacogenetics. 1998 Oct;8(5):383-9. doi: 10.1097/00008571-199810000-00003.
7
Characterization of the cytochrome P450 isoenzymes involved in the in vitro N-dealkylation of haloperidol.参与氟哌啶醇体外N-脱烷基化反应的细胞色素P450同工酶的特性研究。
Br J Clin Pharmacol. 1997 Dec;44(6):557-64. doi: 10.1046/j.1365-2125.1997.t01-1-00629.x.
8
CYP3A is responsible for N-dealkylation of haloperidol and bromperidol and oxidation of their reduced forms by human liver microsomes.
Life Sci. 2000 Nov 3;67(24):2913-20. doi: 10.1016/s0024-3205(00)00874-2.
9
10
Effect of quinidine on the interconversion kinetics between haloperidol and reduced haloperidol in humans: implications for the involvement of cytochrome P450IID6.奎尼丁对人体内氟哌啶醇与还原型氟哌啶醇相互转化动力学的影响：细胞色素P450IID6参与的意义
Eur J Clin Pharmacol. 1993;44(5):433-8. doi: 10.1007/BF00315539.
引用本文的文献
1
Formation of potentially toxic metabolites of drugs in reactions catalyzed by human drug-metabolizing enzymes.药物在人药物代谢酶催化反应中形成潜在毒性代谢物。
Arch Toxicol. 2024 Jun;98(6):1581-1628. doi: 10.1007/s00204-024-03710-9. Epub 2024 Mar 23.
2
Drug-Drug Interactions Between COVID-19 Treatments and Psychotropic Medications: An Updated Study.新型冠状病毒肺炎治疗药物与精神药物之间的药物相互作用：一项更新研究
Cureus. 2023 Dec 13;15(12):e50469. doi: 10.7759/cureus.50469. eCollection 2023 Dec.
3
Automated Interlaboratory Comparison of Therapeutic Drug Monitoring Data and Its Use for Evaluation of Published Therapeutic Reference Ranges.治疗药物监测数据的实验室间自动比对及其在已发表治疗参考范围评估中的应用
Pharmaceutics. 2023 Feb 16;15(2):673. doi: 10.3390/pharmaceutics15020673.
4
Genotyping in Clinical Practice: Ready for Implementation?临床实践中的基因分型：准备好实施了吗？
Front Genet. 2021 Jul 8;12:711943. doi: 10.3389/fgene.2021.711943. eCollection 2021.
5
Human Family 1-4 cytochrome P450 enzymes involved in the metabolic activation of xenobiotic and physiological chemicals: an update.人类家族 1-4 细胞色素 P450 酶参与外源化学物和生理化学物质的代谢激活：更新。
Arch Toxicol. 2021 Feb;95(2):395-472. doi: 10.1007/s00204-020-02971-4. Epub 2021 Jan 18.
6
How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing?药物代谢和转运体遗传学如何为精神药物处方提供信息？
Front Genet. 2020 Dec 8;11:491895. doi: 10.3389/fgene.2020.491895. eCollection 2020.
7
The correlation between CYP2D6 isoenzyme activity and haloperidol efficacy and safety profile in patients with alcohol addiction during the exacerbation of the addiction.酒精成瘾加剧期间，酒精成瘾患者中CYP2D6同工酶活性与氟哌啶醇疗效及安全性之间的相关性。
Pharmgenomics Pers Med. 2016 Sep 14;9:89-95. doi: 10.2147/PGPM.S110385. eCollection 2016.
8
Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, Present and Future.用于治疗精神分裂症的多巴胺靶向药物：过去、现在与未来
Curr Top Med Chem. 2016;16(29):3385-3403. doi: 10.2174/1568026616666160608084834.
9
Association of tardive dyskinesia with variation in CYP2D6: Is there a role for active metabolites?迟发性运动障碍与CYP2D6基因变异的关联：活性代谢产物是否起作用？
J Psychopharmacol. 2014 Jul;28(7):665-70. doi: 10.1177/0269881114523861. Epub 2014 Mar 4.
10
Neuroleptic malignant syndrome in an adolescent with CYP2D6 deficiency.一名患有CYP2D6缺乏症的青少年出现抗精神病药恶性综合征。
Eur J Pediatr. 2014 Dec;173(12):1639-42. doi: 10.1007/s00431-013-2208-z. Epub 2013 Nov 20.
本文引用的文献
1
Determination of 4-(4-chlorophenyl)-4-hydroxypiperidine, a metabolite of haloperidol, by gas chromatography with electron-capture detection.用带电子捕获检测的气相色谱法测定氟哌啶醇的代谢物4-（4-氯苯基）-4-羟基哌啶。
J Chromatogr B Biomed Appl. 1996 Jul 12;682(2):283-8. doi: 10.1016/0378-4347(96)00075-8.
2
Comparison of cytotoxicity of a quaternary pyridinium metabolite of haloperidol (HP+) with neurotoxin N-methyl-4-phenylpyridinium (MPP+) towards cultured dopaminergic neuroblastoma cells.
Psychopharmacology (Berl). 1995 Oct;121(3):373-8. doi: 10.1007/BF02246077.
3
Effect of quinidine on the interconversion kinetics between haloperidol and reduced haloperidol in humans: implications for the involvement of cytochrome P450IID6.奎尼丁对人体内氟哌啶醇与还原型氟哌啶醇相互转化动力学的影响：细胞色素P450IID6参与的意义
Eur J Clin Pharmacol. 1993;44(5):433-8. doi: 10.1007/BF00315539.
4
On the metabolism of haloperidol.关于氟哌啶醇的代谢
Xenobiotica. 1993 May;23(5):495-508. doi: 10.3109/00498259309059390.
5
High-performance liquid chromatographic method for the detection and quantitation of haloperidol and seven of its metabolites in microsomal preparations.
J Chromatogr. 1993 May 5;614(2):267-73. doi: 10.1016/0378-4347(93)80318-x.
6
MPP(+)-like neurotoxicity of a pyridinium metabolite derived from haloperidol: in vivo microdialysis and in vitro mitochondrial studies.氟哌啶醇衍生的吡啶代谢物的MPP(+)样神经毒性：体内微透析和体外线粒体研究
J Pharmacol Exp Ther. 1994 Jan;268(1):380-7.
7
Coadministration of fluvoxamine increases serum concentrations of haloperidol.
J Clin Psychopharmacol. 1994 Oct;14(5):340-3.
8
Distribution, excretion and metabolism of neuroleptics of the butyrophenone type. I. Excretion and metabolism of haloperidol and nine related butyrophenone-derivatives in the Wistar rat.丁酰苯类抗精神病药物的分布、排泄及代谢。I. 氟哌啶醇及九种相关丁酰苯衍生物在Wistar大鼠体内的排泄与代谢
Eur J Pharmacol. 1967 Jan;1(1):47-57. doi: 10.1016/0014-2999(67)90065-9.
9
Extrapyramidal symptoms in a patient taking haloperidol and fluoxetine.
Am J Psychiatry. 1989 Mar;146(3):399-400. doi: 10.1176/ajp.146.3.399b.
10
Identification of a potentially neurotoxic pyridinium metabolite of haloperidol in rats.
Biochem Biophys Res Commun. 1990 Jan 15;166(1):238-44. doi: 10.1016/0006-291x(90)91936-m.
Zotero 插件