Institute of Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Königsweg 67, 14163 Berlin, Germany.
Acta Trop. 2012 Aug;123(2):78-84. doi: 10.1016/j.actatropica.2012.03.008. Epub 2012 Apr 1.
Tribendimidine has been registered for the treatment of human soil transmitted helminthiases in China. In the model nematode Caenorhabditis elegans it is an agonist of L-subtype nicotinic acetylcholine receptors and therefore shares its mode of action with levamisole and pyrantel. Besides its broad spectrum of nematicidal efficacy, tribendimidine is efficacious against several trematodes and has been attributed to have anti-cestodal effects. However, there are few published data available for the latter. The efficacy of tribendimidine and its nematicidal metabolite deacylated amidantel against Hymenolepis microstoma were examined for their anti-cestodal potential. Doses of 50 and 100mg/kg body weight deacylated amidantel and 10, 25, 50, and 100mg/kg tribendimidine were administered orally on three consecutive days to mice experimentally infected with eight cysticercoids. Necropsy was performed and the worm burdens were determined one day after the last treatment. Furthermore, levamisole was used in combination with tribendimidine (100mg/kg levamisole plus 10 and 25mg/kg tribendimidine, respectively) and alone (50 and 100mg/kg) to investigate any possible interactions of the partner compounds against cestodes. Tribendimidine showed a very high efficacy at dosages of 50mg/kg or higher. Surprisingly, deacylated amidantel led to no reduction of the worm burden in any of the treatments. Combinations of levamisole with tribendimidine did not augment the effects of tribendimidine alone and as expected levamisole alone also showed no anti-cestodal activity. To our knowledge, this study shows for the first time activity of tribendimidine against a cestode in a controlled laboratory study. Due to the excellent cure rates observed here, multiple tribendimidine treatments might be considered as useful scheme for treatments of cestode, nematode and trematode infections although this would significantly increase both costs and management efforts. Moreover, the differences between tribendimidine and deacylated amidantel indicate at least a strong difference in sensitivity of H. microstoma or a strong difference in drug availability.
三苯双脒已在中国注册用于治疗人体土源性线虫病。在模式线虫秀丽隐杆线虫中，它是 L 型烟碱型乙酰胆碱受体激动剂，因此与左旋咪唑和噻嘧啶具有相同的作用模式。除了广谱的杀线虫活性外，三苯双脒还对几种吸虫有效，并被认为具有抗囊虫作用。然而，关于后者的发表数据很少。本研究旨在评估三苯双脒及其去酰化 amidantel 对微小膜壳绦虫的抗囊尾蚴作用。在连续三天给感染了 8 个囊尾蚴的实验鼠口服 50 和 100mg/kg 体重的去酰化 amidantel 以及 10、25、50 和 100mg/kg 体重的三苯双脒，剂量分别为 50 和 100mg/kg。在最后一次治疗后一天进行尸检，并确定虫体负荷。此外，还单独使用左旋咪唑（分别为 50 和 100mg/kg）和联合使用（100mg/kg 左旋咪唑加 10 和 25mg/kg 三苯双脒）来研究联合用药对绦虫的可能相互作用。三苯双脒在 50mg/kg 或更高剂量时具有很高的疗效。令人惊讶的是，去酰化 amidantel 在任何治疗中都没有降低虫体负荷。左旋咪唑与三苯双脒联合使用并没有增强三苯双脒的单独作用，正如预期的那样，左旋咪唑单独使用也没有抗绦虫活性。据我们所知，这项研究首次在对照实验室研究中显示了三苯双脒对绦虫的活性。由于这里观察到的治愈率很高，多次使用三苯双脒可能被认为是治疗绦虫、线虫和吸虫感染的有效方案，尽管这将显著增加成本和管理工作。此外，三苯双脒和去酰化 amidantel 之间的差异至少表明微小膜壳绦虫的敏感性差异很大，或者药物的可利用性差异很大。
