INHIBITION OF LYMPHOCYTE PROLIFERATION BY HISTAMINE AND RELATED COMPOUNDS NOT MEDIATED VIA H1‐ OR H2‐ RECEPTORS

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Abstract
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 activity, 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.