HEPATOTOXICITY AND SURFACE-ACTIVITY OF TRICYCLIC ANTI-DEPRESSANTS INVITRO

Cytotoxicity to isolated rat hepatocytes of the tricyclic antidepressants, chlorimipramine, nortriptyline, amitriptyline, imipramine, and of doxepin was determined by the leakage of cytoplasmic and lysosomal enzymes into surrounding media. The rank order of toxicity was: chlorimipramine > nortriptyline > amitriptyline > imipramine > doxepin. All tricyclic antidepressants tested lowered the surface tension of the salt solution contained in the tissue culture media. The rank order of surface activity was the same as that of hepatotoxicity in vitro. These results suggest that the differences in membrane damage produced by tricyclic antidepressants may be related to surface activity which in turn may determine the extent of adsorption onto cell membranes. © 1979.