Akintonwa D A
J Theor Biol. 1984 Jan 7;106(1):79-87. doi: 10.1016/0022-5193(84)90028-6.
The well-known phenomena of enzyme induction and inhibition have been applied in the enunciation of two mechanisms which could be used in the reversal of resistance which organisms develop towards biocides (drugs and pesticides) in many cases. For those biocides active per se which are metabolized by inducible enzymes to non-toxic metabolites, resistant organisms would be those possessing high levels of drug-metabolizing enzymes (Mechanism 1). For those biocides inactive per se but requiring metabolic activation for activity, resistant organisms would be those possessing low levels of drug metabolizing enzymes (Mechanism 2). In mechanism 1, the addition of enzyme inhibitors to the biocide would be effective in reversing resistance. In mechanism 2 the addition of an enzyme inducer to the biocide would increase the susceptibility of the resistant organisms. An ectoparasite insecticide 2-chloro-1-(2,4 dichlorophenyl) vinyl diethylphosphate (chlorfenvinphos or supona) is used as an example for mechanism 1. The malarial drugs primaquine and chloroquine are used as examples of mechanism 2.
酶诱导和抑制这两个著名现象已被用于阐述两种机制，在许多情况下，这两种机制可用于逆转生物体对杀菌剂（药物和杀虫剂）产生的抗性。对于那些本身具有活性但可被诱导酶代谢为无毒代谢物的杀菌剂，抗性生物体将是那些拥有高水平药物代谢酶的生物体（机制1）。对于那些本身无活性但需要代谢激活才能发挥活性的杀菌剂，抗性生物体将是那些拥有低水平药物代谢酶的生物体（机制2）。在机制1中，向杀菌剂中添加酶抑制剂将有效地逆转抗性。在机制2中，向杀菌剂中添加酶诱导剂将增加抗性生物体的敏感性。以一种体外寄生虫杀虫剂2-氯-1-（2,4-二氯苯基）乙烯基二乙基磷酸酯（毒虫畏或苏波纳）作为机制1的示例。抗疟药物伯氨喹和氯喹用作机制2的示例。
