Abstract
Compounds with combined histamine H1- and H2-receptor antagonist activity were synthesized by connecting H1- and H2-receptor substructures via cyanoguanidine, urea, or nitroethenediamine moieties. Loss of the strongly basic side-chain nitrogen results in a decrease of H1-receptor activity compared to single reference compounds. At the guinea-pig right atrium (H2-receptor model) compounds with mepyramine or cyclizine structure are also less active than the single references tiotidine, ranitidine, or lamtidine. Nevertheless substances with a pheniramine like partial structure proved to be potent histamine H2-receptor antagonists at the atrium model (about 27 times more active than cimetidine).
MeSH terms
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Animals
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Cyclizine / analogs & derivatives*
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Cyclizine / chemical synthesis*
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Ethylenediamines / chemistry
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Guanidines / chemical synthesis
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Guanidines / pharmacology
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Guinea Pigs
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Histamine H1 Antagonists / chemical synthesis*
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Histamine H1 Antagonists / pharmacology
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Histamine H2 Antagonists / chemical synthesis*
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Histamine H2 Antagonists / pharmacology
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In Vitro Techniques
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Muscle Contraction / drug effects
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Muscle, Smooth, Vascular / drug effects
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Pheniramine / analogs & derivatives*
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Pheniramine / chemical synthesis*
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Pyrilamine / analogs & derivatives*
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Pyrilamine / chemical synthesis*
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Urea / chemistry
Substances
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Ethylenediamines
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Guanidines
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Histamine H1 Antagonists
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Histamine H2 Antagonists
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Pheniramine
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Urea
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Pyrilamine
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dicyandiamido
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Cyclizine