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New mechanism of plasmid curing by psychotropic drugs.

Methylene blue enhanced the plasmid curing efficiency of chlorpromazine, imipramine and amitriptyline with strains of Escherichia coli K12 carrying F-prime lac or the resistance factor R-144. In contrast, methylene blue inhibited the elimination of plasmids by acridine orange and ethydium bromide at all concentrations tested. Two metabolic derivatives of chlorpromazine, chlorpromazine sulphoxide and 7.8-dioxochlorpromazine had no plasmid curing effect even in the presence of methylene blue. Amitriptyline, 7,8-dioxochlorpromazine and acridine orange were effective inhibitors of the conjugal transfer of the resistance plasmid, R-144, whilst methylene blue, chlorpromazine sulphoxide, and imipramine had only slight effects. We were therefore unable to demonstrate a simple correlation between curing ability and inhibition of plasmid transfer amongst the psychoactive drugs tested. A mechanism of plasmid curing by surface action of the drugs is suggested as an alternative to direct intercalation of the drugs into plasmid DNA.