Effect of phenothiazines, benzo[a] phenothiazines, benz[c]acridines and Pentaglobin on endotoxin.

The endotoxin neutralizing effects of several phenothiazines, benzophenothiazines and Pentaglobin (control) were investigated by spectrophotometry, tumor necrosis factor (TNF) induction and the conventional Limulus test. In animal experiments, some beneficial effects of complex forming compounds were found, however, the compounds could not completely inactivate the biological effect of endotoxin in the Limulus test. The complex formation between endotoxin and the compounds were revealed in spectrophotometry. The TNF inducing effect of compound-endotoxin complexes was markedly reduced by some phenothiazines and benzo[a]phenothiazines in leukocytes. Benz[c]acridines and Pentaglobin could not neutralize completely the TNF induction of E. coli endotoxin. The recent findings indicate that multifocal effects of phenothiazines and benzophenothiazines can be responsible for anti-endotoxin action in vivo. Hypotensive action in experimental animals was reduced by some phenothiazines in some preliminary experiments.