Kovacs J A, Allegra C J, Chabner B A, Swan J C, Drake J, Lunde M, Parrillo J E, Masur H
J Infect Dis. 1987 May;155(5):1027-32. doi: 10.1093/infdis/155.5.1027.
Trimetrexate, a lipid-soluble antifolate, has considerably greater activity in inhibiting the dihydrofolate reductase of Toxoplasma gondii than do the conventional antifolates pyrimethamine and trimethoprim. In an investigation of the effect of trimetrexate on T. gondii, in vitro and in vivo studies were undertaken with peritoneal macrophage cultures and acutely infected mice. Against T. gondii cultured in mouse peritoneal macrophages, 10(-7) M trimetrexate inhibited replication of the organism compared with 10(-6) M pyrimethamine and 10(-4) M trimethoprim. In acutely infected mice, trimetrexate alone prolonged survival and, when combined with sulfadiazine, allowed 93%-100% of mice to survive. These studies suggest that trimetrexate alone or combined with a sulfonamide may provide a safe and effective alternative to pyrimethamine plus sulfonamide for the treatment of T. gondii diseases.
三甲曲沙是一种脂溶性抗叶酸剂，在抑制弓形虫二氢叶酸还原酶方面比传统抗叶酸剂乙胺嘧啶和甲氧苄啶具有更强的活性。在一项关于三甲曲沙对弓形虫作用的研究中，利用腹膜巨噬细胞培养物和急性感染的小鼠进行了体外和体内研究。对于在小鼠腹膜巨噬细胞中培养的弓形虫，10(-7)M的三甲曲沙可抑制该生物体的复制，相比之下，10(-6)M的乙胺嘧啶和10(-4)M的甲氧苄啶才有此效果。在急性感染的小鼠中，单独使用三甲曲沙可延长生存期，与磺胺嘧啶联合使用时，可使93%-100%的小鼠存活。这些研究表明，单独使用三甲曲沙或与磺胺类药物联合使用，可能为治疗弓形虫病提供一种安全有效的替代乙胺嘧啶加磺胺类药物的方法。
