Metabolism of procainamide to a hydroxylamine by human neutrophils and mononuclear leukocytes.
Metabolism of procainamide to a hydroxylamine by human neutrophils and mononuclear leukocytes.
复制标题
人中性粒细胞和单核白细胞将普鲁卡因酰胺代谢为羟胺。
DOI：
10.1021/tx00001a013
复制
发表时间：
1988
影响因子：
4.1
通讯作者：
R. Rubin
中科院分区：
文献类型：
--
作者：
J. Uetrecht;N. Zahid;R. Rubin
长期使用普鲁卡因胺与药物性狼疮和粒细胞缺乏症的高发有关。我们之前已经证明，普鲁胺在肝脏中代谢为活性羟胺（PAHA）和亚硝基（亚硝基- pa）代谢物，它们与蛋白质共价结合，对淋巴细胞有毒。我们提出这些代谢物是普鲁卡因胺毒性的原因。然而，多环芳烃和亚硝基多环芳烃似乎不会以显著的浓度从肝脏中逸出。本文描述了中性粒细胞和单核白细胞将普鲁卡因胺代谢为活性羟胺的过程。这种代谢只有在细胞受到刺激而产生呼吸爆发时才会发生。这些观察结果对普鲁卡因酰胺诱导的粒细胞缺乏症（由中性粒细胞形成反应性代谢物）和普鲁卡因酰胺诱导的狼疮（由单核细胞形成反应性代谢物）的机制可能有明显的影响。单核细胞将药物代谢为反应性代谢物可能是过敏反应的一般机制，因为单核细胞在抗原加工和刺激抗体合成中起着关键作用。
The chronic use of procainamide is associated with a high incidence of drug-induced lupus and also agranulocytosis. We have previously demonstrated that procainamide is metabolized in the liver to reactive hydroxylamine (PAHA) and nitroso (nitroso-PA) metabolites which covalently bind to protein and are toxic to lymphocytes. We proposed that these metabolites were responsible for the toxicities of procainamide. However, PAHA and nitroso-PA do not appear to escape the liver in significant concentrations. In this paper we describe the metabolism of procainamide to a reactive hydroxylamine by neutrophils and mononuclear leukocytes. Such metabolism only occurs if the cells have been stimulated to have a respiratory burst. These observations have obvious possible implications for the mechanism of procainamide-induced agranulocytosis (formation of a reactive metabolite by neutrophils) and procainamide-induced lupus (formation of a reactive metabolite by monocytes). The metabolism of drugs to reactive metabolites by monocytes may be a general mechanism for hypersensitivity reactions because monocytes play a key role in the processing of antigen and stimulation of antibody synthesis.
普鲁卡因酰胺在灌注大鼠肝脏中的代谢。
DOI：
--
发表时间：
1981
期刊：
Drug metabolism and disposition: the biological fate of chemicals
影响因子：
--
作者：
Uetrecht,JP;Woosley,RL;Freeman,RW;Sweetman,BJ;Oates,JA
通讯作者：
Oates,JA
普鲁卡因酰胺羟胺和亚硝基代谢物的反应性和可能的意义。
DOI：
--
发表时间：
1985
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Uetrecht,JP
通讯作者：
Uetrecht,JP
大鼠和人肝微粒体将普鲁卡因酰胺代谢为羟胺。
DOI：
--
发表时间：
1984
期刊：
Drug metabolism and disposition: the biological fate of chemicals
影响因子：
--
作者：
Uetrecht,JP;Sweetman,BJ;Woosley,RL;Oates,JA
通讯作者：
Oates,JA