Edlind T D, Hang T L, Chakraborty P R
Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia 19129.
J Infect Dis. 1990 Dec;162(6):1408-11. doi: 10.1093/infdis/162.6.1408.
In vitro growth of the protozoan parasite Giardia lamblia was highly sensitive to certain anthelmintic benzimidazoles. Albendazole and mebendazole were 30- to 50-fold more active than metronidazole and 4- to 40-fold more active than quinacrine. Thiabendazole, a noncarbamate benzimidazole, was less active. Since lack of intestinal absorption makes mebendazole an attractive new antigiardial agent, its in vitro activity was further characterized. At low concentrations (0.05 micrograms/ml) mebendazole had a static effect on G. lamblia growth; however, lethal activity was observed at a concentration fivefold lower (0.3 micrograms/ml) than necessary for the cidal agent metronidazole. Two observations are consistent with a microtubule target for mebendazole. First, attachment of cells to the culture tube, mediated by the ventral disk and flagella, was rapidly disrupted by mebendazole treatment. Second, the characteristic cell structure was grossly distorted by treatment. No mebendazole-resistant G. lamblia were detected in a population of 10(8) cells.
原生动物寄生虫蓝氏贾第鞭毛虫的体外生长对某些抗蠕虫苯并咪唑高度敏感。阿苯达唑和甲苯达唑的活性比甲硝唑高30至50倍,比喹吖因高4至40倍。噻苯达唑,一种非氨基甲酸酯类苯并咪唑,则活性较低。由于肠道吸收不良使甲苯达唑成为一种有吸引力的新型抗贾第虫药物,因此对其体外活性进行了进一步表征。在低浓度(0.05微克/毫升)时,甲苯达唑对蓝氏贾第鞭毛虫的生长有静态作用;然而,观察到致死活性的浓度比杀微生物剂甲硝唑所需浓度低五倍(0.3微克/毫升)。有两项观察结果与甲苯达唑的微管靶点一致。第一,由腹盘和鞭毛介导的细胞与培养管的附着被甲苯达唑处理迅速破坏。第二,处理后特征性细胞结构严重扭曲。在10⁸个细胞群体中未检测到耐甲苯达唑的蓝氏贾第鞭毛虫。