Effect of analogs of cinanserin on human lymphocytes in vitro.

Cinanserin, 2′-(3-dimethylaminopropylthio)cinnamanilide, was compared in phytohemagglutinin (PHA)-treated human lymphocytes in vitro to two analogs, 2′-(3-dimethylaminopropoxy)-5′-methylcinnamanilide (SQ 11,276) and 5′- tert.-butyl-2′-(3-dimethylaminopropoxy) cinnamanilide (SQ 11,332). These analogs, like cinanserin, exhibit immunosuppressive activity but, unlike cinanserin, possess low antiserotonin activity. Within 1-1.5 hours after addition of the drugs (0.15 m M), incorporation ofH-uridine,C-leucine, andH-thymidine into a macromolecular fraction of PHA-treated cells were inhibited, in an increasing order, by cinanserin, SQ 11,276 and SQ 11,332. At this concentration cellular recovery and viability wre unaltered by cinanserin and SQ 11,276 and substantially decreased by SQ 11,332. SQ 11,332 was less cytotoxic at lower concentrations and 4-7 times more active than cinanserin as an inhibitor of the incorporation of the nucleosides into the macromolecular fraction. [ABSTRACT FROM AUTHOR]