Godin C S, Crooks P A
College of Pharmacy, University of Kentucky, Lexington 40536-0082.
Drug Metab Dispos. 1989 Mar-Apr;17(2):180-5.
The biotransformation of 4-phenylpyridine and 4,4'-bipyridyl to N-methylated quaternary ammonium metabolites in guinea pig and rabbit has been examined. Neither animal species excreted the neurotoxin N-methyl-4-phenylpyridinium ion as a urinary metabolite after ip administration of 4-phenylpyridine. However, treatment of rabbits with 4,4'-bipyridyl resulted in the formation of N-methyl-4,4'-bipyridinium ion in the urine (1.2% of the administered dose), and ip administration of 4,4'-bipyridyl to guinea pigs afforded both N-methyl-4,4'-bipyridinium ion and N,N'-dimethyl-4,4'-bipyridinium ion (paraquat) as urinary metabolites (0.8% and 2.9%, respectively, of the administered dose). The detection of the lung toxin paraquat as a urinary metabolite of 4,4'-bipyridyl is a significant finding, in that it represents the first documented report of the formation of a toxic metabolite via the N-methylation pathway.
已对豚鼠和兔子体内4-苯基吡啶和4,4'-联吡啶向N-甲基化季铵代谢物的生物转化进行了研究。腹腔注射4-苯基吡啶后，两种动物均未将神经毒素N-甲基-4-苯基吡啶离子作为尿液代谢物排出。然而，用4,4'-联吡啶处理兔子会导致尿液中形成N-甲基-4,4'-联吡啶离子（占给药剂量的1.2%），对豚鼠腹腔注射4,4'-联吡啶则产生N-甲基-4,4'-联吡啶离子和N,N'-二甲基-4,4'-联吡啶离子（百草枯）作为尿液代谢物（分别占给药剂量的0.8%和2.9%）。检测到百草枯这种肺部毒素作为4,4'-联吡啶的尿液代谢物是一项重要发现，因为这是通过N-甲基化途径形成有毒代谢物的首个文献报道。
