人源和鼠源肝微粒体酶对氰化物解毒剂 4-氨基苯丙酮（4-PAPP）的生物活化：抑制剂的影响。
Bioactivation of the cyanide antidote 4-aminopropiophenone (4-PAPP) by human and rat hepatic microsomal enzymes: effect of inhibitors.
机构信息
Mechanisms of Drug Toxicity Group, Pharmaceutical Sciences Institute, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
出版信息
Environ Toxicol Pharmacol. 1999 Mar;7(1):75-80. doi: 10.1016/s1382-6689(98)00052-0.
The bioactivation of the cyanide antidote methaemoglobin former 4-aminopropiophenone (4-PAPP) was studied using rat and human microsomes. With rat liver and NADPH in single and two-compartment systems, dapsone and benzocaine were more potent methaemoglobin generators compared with 4-PAPP. In the single compartment studies, the order of potency of inhibition of 4-PAPP-mediated methaemoglobin formation was cimetidine (1.5 mM)>isoniazid (500 μM)/diethyldithiocarbamate (DDC, 1 mM)>erythromycin (500 μM). Human liver microsomal activation of 4-PAPP in the two-compartment system was partially inhibited by both DDC and cimetidine. These preliminary studies suggest that 4-PAPP may be metabolised by CYP 2C11, 2E1 and 3A in the rat and CYP 2C, 2E1 and probably 3A4 in man.
本文研究了氰化物解毒剂高铁血红蛋白形成剂 4-氨基苯丙酮（4-PAPP）在大鼠和人肝微粒体中的生物活化作用。在大鼠肝微粒体和 NADPH 的单相和双相系统中，与 4-PAPP 相比，达普司酮和苯佐卡因是更有效的高铁血红蛋白生成剂。在单相研究中，4-PAPP 介导的高铁血红蛋白形成抑制的效力顺序为西咪替丁（1.5mM）＞异烟肼（500μM）/二乙基二硫代氨基甲酸盐（DDC，1mM）＞红霉素（500μM）。人肝微粒体在双相系统中对 4-PAPP 的激活部分被 DDC 和西咪替丁抑制。这些初步研究表明，4-PAPP 可能在大鼠中被 CYP2C11、2E1 和 3A 代谢，在人中被 CYP2C、2E1 和可能的 3A4 代谢。
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