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The clastogenic effects of imipramine on chromosomes have been investigated in leukocyte cultures from seven healthy blood donors (2 mlae and 5 female), repeat cultures being initiated at intervals of 6 to 12 weeks. At various times prior to harvesting nine different doses of imipramine were added in vitro, the three lowest concentrations being within the range of plasma levels reported in psychiatric patients reveiving the drug therapeutically. In addition, streptonigrin was used as a positive control. No increase in chromosome breaks was found at any concentration for any duration of exposure even in those cultures where high concentration and/or long duration of exposure significantly suppressed cell growth. Only cultures to which streptonigrin had been added showed a significant increase in chromosome breaks.

The effects of imipramine hydrochloride on cell proliferation were investigated in leukocyte cultures derived from normal volunteers. Nine different doses of imipramine were added in vitro at random for 4, 24, 48, and 68 hours, the three lowest concentrations being within the range of plasma levels reported in psychiatric patients receiving the drug therapeutically. Cell proliferations, as measured by mitotic index, was affected by both the concentration and the duration of drug exposure; the higher the dose and/or the longer the drug in culture, the lower the mitotic index. Imipramine concentrations corresponding to therapeutic plasma levels had no effect on mitotic index regardless of the length of exposure.