Reduced cell survival and morphological alterations induced by three tricyclic antidepressants in human peripheral monocytes and lymphocytes and in cell lines derived from these cell types

Tricyclic antidepressant drugs are widely used for the treatment of manic-depressive disorders. As such compounds have been reported to give rise to myelin figures in lymphocytes in experimental animals, the effects of clomipramine (2.5-50 mu M), imipramine (2.5-100 mu M) and citalopram (5-50 mu M) on human peripheral lymphocytes, granulocytes and monocytes in culture were investigated. No cytoplasmic alterations were detected in T or B lymphocytes, but large myelin figures could be seen by fluorescence and electron microscopy in monocytes. Optimal concentrations for the formation of these structures were 20 mu M for clomipramine and 40 mu M for imipramine. A strongly dose-dependent inhibition of the growth of Molt-4 and U937 cells was also observed with clomipramine, which was 2.5-fold as potent as imipramine in this respect. Treated U937, but not Molt-4, cells showed an increased content of fluorescent granules compared with untreated cells. Furthermore, these tricyclic antidepressants appeared to induce apoptosis in lymphocytes, as judged from the disorganization of the nucleus and the appearance of a typical DNA ladder pattern in treated cells. (C) 1997 Elsevier Science Ltd.