Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Bari, Italy.
Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
Pharmacol Rep. 2021 Feb;73(1):172-184. doi: 10.1007/s43440-020-00167-2. Epub 2020 Oct 19.
Lubeluzole, a neuroprotective anti-ischemic drug, was tested for its ability to act as both antibiotic chemosensitizing and antipropulsive agent for the treatment of infectious diarrhea.
In the present report, the effect of lubeluzole against antidiarrheal target was tested. The antimicrobial activity towards Gram-positive and Gram-negative bacteria was investigated together with its ability to affect ileum and colon contractility.
Concerning the antimicrobial activity, lubeluzole showed synergistic effects when used in combination with minocycline against four common Gram-positive and Gram-negative bacteria (Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922), although relatively high doses of lubeluzole were required. In ex vivo experiments on sections of gut smooth muscles, lubeluzole reduced the intestinal contractility in a dose-dependent manner, with greater effects observed on colon than on ileum, and being more potent than reference compounds otilonium bromide and loperamide.
All above results identify lubeluzole as a possible starting compound for the development of a novel class of antibacterial adjuvants endowed with spasmolytic activity.
神经保护抗缺血药物卢比洛芬,因其具有作为抗生素增敏和抗推进剂的双重作用,被用于治疗感染性腹泻。
本研究报告测试了卢比洛芬对止泻靶点的作用。研究了其对革兰氏阳性和革兰氏阴性细菌的抗菌活性,以及对回肠和结肠收缩性的影响。
关于抗菌活性,卢比洛芬与米诺环素联合使用时,对四种常见的革兰氏阳性和革兰氏阴性菌(粪肠球菌 ATCC 29212、金黄色葡萄球菌 ATCC 29213、铜绿假单胞菌 ATCC 27853 和大肠杆菌 ATCC 25922)表现出协同作用,尽管需要较高剂量的卢比洛芬。在肠道平滑肌切片的离体实验中,卢比洛芬呈剂量依赖性地降低肠道收缩性,对结肠的影响大于回肠,且比参考化合物奥替溴铵和洛哌丁胺更有效。
所有上述结果表明,卢比洛芬可能是一种新型具有解痉活性的抗菌佐剂的起始化合物。