A COMPARISON OF DIMAPRIT, NORDIMAPRIT, METHYLAMINE AND CHLOROQUINE AS INHIBITORS OF MITOGEN-INDUCED LYMPHOCYTE-ACTIVATION

Methylamine and chloroquine, both lysosomotropic agents (i.e., agents which sequester in lysosomes), caused a dose-related inhibition of mitogen-induced human lymphocyte activation in the concentrations which previously increased the pH of lysosomes. The dose-response curves of inhibition of mitogen-induced lymphocyte activation for chloroquine and methylamine were very steep and were similar to the dose-response curves contained with dimaprit and nordimaprit, but very different from the flat dose-response curves previously described for histamine. Approximate IC50 [median inhibitory concentration] values were methylamine 6.4 mM, dimaprit 0.13 mM, nordimaprit 0.03 mM and chloroquine 18 .mu.M. The mechanism of action of methylamine and chloroquine may be related to their lysosomotropic action and consequent interference with ligand-receptor processing, and dimaprit and nordimaprit but not histamine may act by a similar mechanism.