Yuthavong Y, Panijpan B, Ruenwongsa P, Sirawaraporn W
Southeast Asian J Trop Med Public Health. 1985 Sep;16(3):459-72.
Biochemical aspects of action of antifolates and 4-aminoquinolines and their resistance in the malaria parasites are reviewed, with emphasis on pyrimethamine and chloroquine respectively. Resistance to pyrimethamine has been shown to be associated with either an increase in the amount of parasite dihydrofolate reductase or a reduced affinity of the enzyme for drug binding, in line with the presence of a distinctive pathway for folate metabolism. The theories for drug synergism in the folate pathway are discussed with respect to resistance to pyrimethamine and its combination with sulpha drugs. The biochemical basis for chloroquine resistance is still unclear, reflecting incomplete understanding of its mechanism of action. Data implicating the role of haemozoin and other components as a putative chloroquine receptor of the parasites are reviewed, and possible explanations for resistance are discussed.
本文综述了抗叶酸剂和4-氨基喹啉类药物的作用及其在疟原虫中的耐药性的生化方面，重点分别是乙胺嘧啶和氯喹。已证明对乙胺嘧啶的耐药性与疟原虫二氢叶酸还原酶量的增加或该酶与药物结合的亲和力降低有关，这与叶酸代谢存在独特途径一致。讨论了叶酸途径中药物协同作用的理论，涉及对乙胺嘧啶的耐药性及其与磺胺类药物的联合使用。氯喹耐药性的生化基础仍不清楚，这反映出对其作用机制的理解不完整。综述了提示疟色素和其他成分作为寄生虫假定氯喹受体作用的数据，并讨论了耐药性的可能解释。
