Interaction between tricyclic psychopharmacons and some antibiotics.

The tricyclic psychopharmacons, e.g. clozapine, promethazine and imipramine cure plasmids and inhibit plasmid transfer among bacteria due to the inhibition of supercoiling activity on DNA gyrase. In addition an interaction was found between clozapine, imipramine, promethazine and some antibiotics, e.g. penicillins and tetracycline in vitro. The nature of interaction is based on a charge transfer complex, which is formed between clozapine, imipramine, promethazine and penicillins. Differential spectrophotometry showed that ampicillin reduced the highest energy peaks of clozapine, promethazine and imipramine. Streptomycin did not alter the spectrum of clozapine; however, tetracycline somewhat reduced all the peaks of clozapine. Clozapine and promethazine exhibited a synergistic effect with ampicillin, tetracycline and gentamicin on Escherichia coli cells in in vitro. This kind of interaction was missing in the case of imipramine.