Metabolic defects caused by treatment with the tetrahydropyridine analog of haloperidol (HPTP), in baboons.
Metabolic defects caused by treatment with the tetrahydropyridine analog of haloperidol (HPTP), in baboons.
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DOI：
10.1016/s0024-3205(97)00382-2
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发表时间：
1997-06
期刊：
影响因子：
6.1
通讯作者：
L. Mienie;J. Bergh;E. van Staden;S. Steyn;S. Pond;N. Castagnoli;C. J. Van der Schyf
中科院分区：
文献类型：
--
作者：
L. Mienie;J. Bergh;E. van Staden;S. Steyn;S. Pond;N. Castagnoli;C. J. Van der Schyf
越来越多的证据表明，细胞能量产生受损是特发性和药物诱导的退化过程的主要贡献者。我们对神经毒素的兴趣促使我们研究了HPTP对反映线粒体呼吸缺陷的尿液化学标志物的影响。HPTP是氟哌啶醇的四氢吡啶脱水产物。尿液中的二元酸和结合物谱，类似于人类线粒体代谢先天缺陷和毒素诱导的牙买加呕吐病(JVS)，在处理后的狒狒中观察到。我们将这些结果解释为HPTP和/或HPTP代谢物抑制狒狒线粒体呼吸的证据，并推测类似的影响可能发生在氟哌啶醇治疗的个体中。
Mounting evidence suggests that compromised cellular energy production is a major contributor to idiopathic and drug-induced degenerative processes. Our interest in neurotoxins have prompted us to examine in the baboon the effects of HPTP, the tetrahydropyridine dehydration product of haloperidol, on urinary chemical markers that reflect defects in mitochondrial respiration. Urinary dicarboxylic acid and conjugate profiles, similar to those seen in humans with inborn errors of mitochondrial metabolism and toxin-induced Jamaican vomiting sickness (JVS) were observed in the treated baboons. We interpret these results as evidence that HPTP and/or HPTP metabolites inhibit mitochondrial respiration in the baboon and speculate that analogous effects may occur in haloperidol-treated individuals.