McCann P P, Bacchi C J, Clarkson A B, Seed J R, Nathan H C, Amole B O, Hutner S H, Sjoerdsma A
Med Biol. 1981 Dec;59(5-6):434-40.
DL-alpha-Difluoromethylornithine (DFMO), a specific enzyme-activated irreversible inhibitor of ornithine decarboxylase (ODC) was previously shown to cure mice infected with Trypanosoma brucei brucei, a parasite of game and cattle in Africa and Trypanosoma brucei rhodesiense, a human African Sleeping Sickness pathogen. Our studies now indicate that DFMO blocks ornithine decarboxylase and lowers trypanosome polyamine levels in vivo. Polyamine uptake in T.b. brucei also resembles that previously described for mammalian cells. The therapeutic potential of DFMO can now also be extended to another human pathogen, Trypanosoma brucei gambiense. Finally, DFMO acts synergistically with another drug, bleomycin, to cure acute trypanosome infections, and furthermore, this same drug combination provides a new approach to the treatment of trypanosomal infections of the central nervous system.
DL-α-二氟甲基鸟氨酸（DFMO）是鸟氨酸脱羧酶（ODC）的一种特异性酶激活不可逆抑制剂，此前已证明它能治愈感染了布氏布氏锥虫（一种非洲野生动物和牛的寄生虫）以及罗德西亚布氏锥虫（一种人类非洲昏睡病病原体）的小鼠。我们现在的研究表明，DFMO在体内可阻断鸟氨酸脱羧酶并降低锥虫的多胺水平。布氏布氏锥虫对多胺的摄取也与先前描述的哺乳动物细胞相似。DFMO的治疗潜力现在还可以扩展到另一种人类病原体——冈比亚布氏锥虫。最后，DFMO与另一种药物博来霉素协同作用，可治愈急性锥虫感染，此外，这种相同的药物组合为治疗中枢神经系统的锥虫感染提供了一种新方法。
