Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98, Kasugade-naka, Konohana-ku, Osaka 554, Japan.
Environ Toxicol Pharmacol. 1996 Dec 20;2(4):331-7. doi: 10.1016/s1382-6689(96)00066-x.
Empenthrin, synthetic pyrethroid, prolonged the pentobarbital-induced sleeping time in mice, but not in rats, guinea pigs or hamsters. Empenthrin did not delay the clearance of pentobarbital from serum in dogs. In addition, empenthrin dose-dependently inhibited in vitro metabolism of pentobarbital in mice, but not in rats, guinea pigs, hamsters or rabbits. Lineweaver-Burk plots indicated that the inhibition was competitive in mice. Microsomal fractions of recombinant yeast expressing human cytochrome P-450 (CYP)s were used to determine the inhibitory effect of empenthrin on pentobarbital metabolism in humans. CYP2B6 and CYP2D6 were responsible for biotransformation of pentobarbital to a pentobarbital alcohol identified as 5-ethyl-5-(1'-methyl-3'-hydroxybutyl) barbituric acid. The structure of pentobarbital fit the criteria for a CYP2D6 substrate on computational analysis. Empenthrin did not inhibit the pentobarbital metabolism catalyzed by these two CYPs. These findings suggest that the inhibition of pentobarbital metabolism by empenthrin in mice does not occur in other species including humans.
氯菊酯，一种合成的拟除虫菊酯，可延长戊巴比妥诱导的小鼠睡眠时间，但对大鼠、豚鼠或仓鼠则无此作用。氯菊酯不会延迟戊巴比妥在狗血清中的清除。此外，氯菊酯可剂量依赖性地抑制小鼠体内戊巴比妥的体外代谢，但对大鼠、豚鼠、仓鼠或家兔则无此作用。Lineweaver-Burk 作图表明这种抑制作用在小鼠体内是竞争性的。用人细胞色素 P-450（CYP）表达的重组酵母的微粒体部分，以确定氯菊酯对人类戊巴比妥代谢的抑制作用。CYP2B6 和 CYP2D6 负责将戊巴比妥生物转化为鉴定为 5-乙基-5-（1'-甲基-3'-羟基丁基）巴比妥酸的戊巴比妥醇。戊巴比妥的结构符合计算分析得出的 CYP2D6 底物的标准。氯菊酯对这两种 CYP 催化的戊巴比妥代谢没有抑制作用。这些发现表明，在包括人类在内的其他物种中，氯菊酯并不抑制戊巴比妥在小鼠体内的代谢。
