Silver E H, Kuttab S H, Hasan T, Hassan M
Drug Metab Dispos. 1982 Sep-Oct;10(5):495-8.
In order to investigate structure-activity relationships that influence metabolism of nitriles to CN-, thiocyanate was measured, as an index of CN- release, in urine of rats given equimolar doses of nitriles. Significantly more SCN- was excreted after po than after ip administration of saturated (C2-C5) nitriles, but SCN- excretion was the same after both routes for n-hexanenitrile. Among saturated nitriles, SCN- excretion was maximal for the C3 and C4 compounds, propionitrile, n-butyronitrile, and isobutyronitrile, after both po and ip administration. SCN- excretion was not elevated after administration of the tertiary nitrile trimethylacetonitrile. Administration (po) of the unsaturated nitriles acrylonitrile, crotonitrile, and 3-butenenitrile yielded 37%, 5.6%, and 29% of the dose as SCN-, whereas after ip injection 4.5%, 4.6%, and 18% of the doses were excreted as SCN-, respectively. After iv injection of acrylonitrile, urinary SCN- content was not elevated, whereas 45% of an iv dose of the saturated analog propionitrile was excreted as SCN-. These results suggest that length of the carbon chain, presence of substituents at the alpha-carbon, position of double bonds, and, for some compounds, route of administration, are important factors influencing the release of CN- from nitriles.
为了研究影响腈代谢为氰离子（CN⁻）的构效关系，在给大鼠给予等摩尔剂量的腈后，测定其尿液中的硫氰酸盐（作为CN⁻释放的指标）。口服给予饱和（C2 - C5）腈后排出的硫氰酸盐（SCN⁻）显著多于腹腔注射，但正己腈经两种给药途径后SCN⁻排泄量相同。在饱和腈中，口服和腹腔注射后，C3和C4化合物（丙腈、正丁腈和异丁腈）的SCN⁻排泄量最大。给予叔丁腈三甲基乙腈后，SCN⁻排泄量未升高。口服给予不饱和腈丙烯腈、巴豆腈和3 - 丁烯腈后，分别有37%、5.6%和29%的剂量以SCN⁻形式排出，而腹腔注射后，分别有4.5%、4.6%和18%的剂量以SCN⁻形式排出。静脉注射丙烯腈后，尿液中SCN⁻含量未升高，而静脉注射饱和类似物丙腈后，45%的剂量以SCN⁻形式排出。这些结果表明，碳链长度、α - 碳上取代基的存在、双键位置以及某些化合物的给药途径是影响腈释放CN⁻的重要因素。
