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.
D000165:Acridine Orange / Q000494:pharmacology; D000639:Amitriptyline / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology*; D003227:Conjugation, Genetic / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics; D004996:Ethidium / Q000494:pharmacology; D005144:F Factor / Q000187:drug effects*; D007099:Imipramine / Q000494:pharmacology*; D008751:Methylene Blue / Q000494:pharmacology; D011815:R Factors / Q000187:drug effects*
D000639:Amitriptyline; D004996:Ethidium; D000165:Acridine Orange; D007099:Imipramine; D008751:Methylene Blue; D002746:Chlorpromazine