SYNTHESIS AND COMBINED HISTAMINE H1-RECEP TOR AND H2-RECEPTOR ANTAGONIST ACTIVITY OF MEPYRAMINE, PHENIRAMINE, AND CYCLIZINE DERIVATIVES WITH CYANOGUANIDINE, UREA, AND NITROETHENEDIAMINE GROUPS

Compounds with combined histamine H-1- and H-2-receptor antagonist act ivity were synthesized by connecting H-1- and H2-receptor substructure s via cyanoguanidine, urea, or nitroethenediamine moieties. Loss of th e strongly basic side-chain nitrogen results in a decrease of H-1-rece ptor activity compared to single reference compounds. At the guinea-pi g right atrium (H-2-receptor model) compounds with mepyramine or cycli zine structure are also less active than the single references tiotidi ne, ranitidine, or lamtidine. Nevertheless substances with a phenirami ne like partial structure proved to be potent histamine H-2-receptor a ntagonists at the atrium model (about 27 times more active than cimeti dine).