Prevention of the emergence of drug resistance in bacteria by acridines, phenothiazines, and dibenzocycloheptenes.

It has been found that, like Atabrine, the phenothiazine tranquilizers promazine, chlorpromazine, promethazine, levopromethazine, and Stelazine; the antidepressants (dibenz-azepine and dibenzocycloheptene derivatives) Tofranil, Pertofrane, cyclobenzaprine, Elavil, protriptyline, and 3-chlorodibenzocycloheptene; and the acridine derivatives acridine orange, acriflavin, SKF no. 16214-A2, SKF no. 13231-A2, SKF no. 9200, and SKF no. 9836 are all to a greater or lesser extent than Atabrine, effective in preventing the emergence of resistant strains of Staphylococcus aureus and Escherichia coli in the presence of streptomycin, sulfathiazole, or chloramphenicol. The antimalarials chloroquine and hydroxychloroquine were also studied and found to be ineffective. The medical significance of these findings is discussed, as well as the effect of the structural variations of these compounds on their relative activities.