Protective effect of muramyl dipeptide analogs against infections of Pseudomonas aeruginosa or Candida albicans in mice.
Two analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide) were found to give better protection than muramyl dipeptide against intraperitoneal Pseudomonas aeruginosa infection or intravenous Candida albicans infection in mice. The analogs tested were N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine and N-acetylmuramyl-L-alpha-amino-butyryl-D-isoglutamine. The optimum treatment was 80 mg/kg per day given once daily for 4 consecutive days before infection by the intraperitoneal, intravenous, or subcutaneous route. Dose response was limited. The compounds were not orally active. Synergism was seen between N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine and gentamicin. No postinfection protection was observed. A nonspecific stimulation of macrophage cells by muramyl dipeptide analogs may contribute to the protection because antiinfective activity against Listeria monocytogenes given intraperitoneally was achieved with CBA mice.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives; D000818:Animals; D002177:Candidiasis / Q000276:immunology*; D005260:Female; D005839:Gentamicins / Q000627:therapeutic use; D006020:Glycopeptides / Q000276:immunology*; D051379:Mice; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000276:immunology*; D013329:Structure-Activity Relationship; D013997:Time Factors
D005839:Gentamicins; D006020:Glycopeptides; D000119:Acetylmuramyl-Alanyl-Isoglutamine