Vol.:(0123456789) 1 3 Pharmacological Reports https://doi.org/10.1007/s43440-020-00167-2 ARTICLE Lubeluzole: from anti‑ischemic drug to preclinical antidiarrheal studies Maria Maddalena Cavalluzzi 1  · Roberta Budriesi 2  · Maria Antonietta De Salvia 3  · Laura Quintieri 4  · Monica Piarulli 1  · Gualtiero Milani 1  · Roberta Gualdani 5  · Matteo Micucci 2  · Ivan Corazza 6  · Antonio Rosato 1  · Maurizio Viale 7  · Leonardo Caputo 4  · Carlo Franchini 1  · Giovanni Lentini 1 Received: 27 July 2020 / Revised: 21 September 2020 / Accepted: 25 September 2020 © Maj Institute of Pharmacology Polish Academy of Sciences 2020 Abstract Background Lubeluzole, a neuroprotective anti-ischemic drug, was tested for its ability to act as both antibiotic chemosen- sitizing and antipropulsive agent for the treatment of infectious diarrhea. Methods In the present report, the efect of lubeluzole against antidiarrheal target was tested. The antimicrobial activ- ity towards Gram-positive and Gram-negative bacteria was investigated together with its ability to afect ileum and colon contractility. Results Concerning the antimicrobial activity, lubeluzole showed synergistic efects when used in combination with mino- cycline against four common Gram-positive and Gram-negative bacteria (Enterococcus faecalis ATCC 29212, Staphylococ- cus 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 efects observed on colon than on ileum, and being more potent than reference compounds otilonium bromide and loperamide. Conclusion All above results identify lubeluzole as a possible starting compound for the development of a novel class of antibacterial adjuvants endowed with spasmolytic activity. Graphic abstract Keywords Lubeluzole · Diarrhoea · Ion channels · Antibiotics · Synergism · Gut contractility Abbreviations Ach Acetylcholine ATCC American Type Culture Collection BSCA Basal spontaneous contraction activity CaM Calmodulin Electronic supplementary material The online version of this article (https://doi.org/10.1007/s43440-020-00167-2) contains supplementary material, which is available to authorized users. Extended author information available on the last page of the article