Inhibition of biological effects of endotoxins by phenothiazines.
The importance of change transfer reaction involving endotoxins of bacteria and interactions between endotoxin-induced tumor necrosis factor (TNF) were investigated both in vitro and in vivo in the presence of several phenothiazines. Complex formation between endotoxins and ring-substituted phenothiazines, benzodiazepines, amantadine and promethazine was measured using spectrophotometric methods. The endotoxin-induced hypotensive effect was prevented by phenothiazine pretreatment of the dogs; however, the endotoxin-phenothiazine complex had the same effect as the endotoxin itself. The tumor necrosis factor-inducing ability of endotoxin in human monocytes was prevented by promethazine. The TNF induction by endotoxin was inhibited by promethazine in vivo.
Molnár
J
J
Institute of Microbiology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Mandi
Y
Y
Regely
K
K
Tarnoky
K
K
Nakamura
M J
MJ
D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D003864:Depression, Chemical; D004285:Dogs; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007022:Hypotension / Q000139:chemically induced; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D015394:Molecular Structure; D010640:Phenothiazines / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004731:Endotoxins; D008070:Lipopolysaccharides; D010640:Phenothiazines; D014409:Tumor Necrosis Factor-alpha; D001569:Benzodiazepines; D000547:Amantadine; D007213:Indomethacin