Inhibition of lymphocyte proliferation by histamine and related compounds not mediated via H1- or H2- receptors.

1 The effects of histamine and chemical analogues were examined on mitogen-stimulated human lymphocyte proliferation. 2 Compounds with selective agonist activity at either H1- or H2-receptors were found to inhibit proliferative responses, although N-3-methyl-histamine which does not act on either receptor was as inhibitory as histamine itself. 3 The H2-receptor agonist, dimaprit, had a profound inhibitory effect on proliferation, however nordimaprit, which has little or no H2-agonist activitiy, was more active on lymphocytes. Impromidine, although a potent H2-agonist, failed to produce such inhibition. 4 The effects of dimaprit and nordimaprit were not reversed by H2-receptor antagonists, cimetidine or metiamide. 5 These results do not support the view that the antiproliferative effects of histamine and related compounds are mediated via conventional H1-or H2-receptors. 6 SKF 93390 was found to be the most active of the dimaprit analogues tested, which could represent a novel series of potential immunosuppressive agents.