Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720-3112, United States.
J Agric Food Chem. 2013 Aug 21;61(33):7883-8. doi: 10.1021/jf4030695. Epub 2013 Aug 7.
Cycloxaprid (CYC) is a novel neonicotinoid prepared from the (nitromethylene)imidazole (NMI) analogue of imidacloprid. In this study we consider whether CYC is active per se or only as a proinsecticide for NMI. The IC50 values (nM) for displacing [(3)H]NMI binding are 43-49 for CYC and 2.3-3.2 for NMI in house fly and honeybee head membranes and 302 and 7.2, respectively, in mouse brain membranes, potency relationships interpreted as partial conversion of some CYC to NMI under the assay conditions. The 6-8-fold difference in toxicity of injected CYC and NMI to house flies is consistent with their relative potencies as in vivo nicotinic acetylcholine receptor (nAChR) inhibitors in brain measured with [(3)H]NMI binding assays. CYC metabolism in mice largely involves cytochrome P450 pathways without NMI as a major intermediate. Metabolites of CYC tentatively assigned are five monohydroxy derivatives and one each of dihydroxy, nitroso, and amino modifications. CYC appears be a proinsecticide, serving as a slow-release reservoir for NMI with selective activity for insect versus mammalian nAChRs.
环吡丙醚（CYC）是一种新型烟碱类杀虫剂，由吡虫啉的（亚硝基甲基）咪唑（NMI）类似物制备而成。在这项研究中，我们考虑 CYC 本身是否具有活性，或者只是 NMI 的前体杀虫剂。在家蝇和蜜蜂头部膜中，[（3）H]NMI 结合的 CYC 和 NMI 的 IC50 值（nM）分别为 43-49 和 2.3-3.2，而在鼠脑膜中，分别为 302 和 7.2，这些结果被解释为在检测条件下，部分 CYC 转化为 NMI。注射 CYC 和 NMI 对家蝇的毒性差异 6-8 倍，与它们作为脑内尼古丁乙酰胆碱受体（nAChR）抑制剂的相对效力一致，这是通过[（3）H]NMI 结合测定来测量的。在小鼠中，CYC 的代谢主要涉及细胞色素 P450 途径，而 NMI 不是主要的中间产物。暂定分配的 CYC 代谢物有五个单羟基衍生物和一个二羟基、亚硝基和氨基修饰物。CYC 似乎是一种前体杀虫剂，作为 NMI 的缓慢释放储库，对昆虫和哺乳动物 nAChR 具有选择性活性。
