title: Evidence that tamoxifen is a histamine antagonist.
abstract: Recently we reported that both the triphenylethylene antiestrogen tamoxifen, and the novel compound N,N-diethyl-2-[(4 phenylmethyl)-phenoxy]-ethanamine. HCl (DPPE), which is selective for the antiestrogen binding site, may be histamine antagonists and have suggested that the antiestrogen binding site may be a growth-promoting histamine receptor different from H1 and H2 (?H3). We now show that along with established H1-antagonists, tamoxifen and DPPE specifically block the histamine-induced (H1) contraction of canine tracheal smooth muscle in the order: pyrilamine = hydroxyzine greater than tamoxifen = 4-hydroxytamoxifen greater than DPPE. The H1-antagonist hydroxyzine, which competes about equally with DPPE for the antiestrogen binding site, is up to 10(3) times stronger than DPPE in blocking histamine-induced muscle contraction. This shows that H1 antagonism is distinct from binding to the antiestrogen binding site and suggests that if the latter is a histamine receptor, it is not H1; presumably tamoxifen and DPPE compete for this novel site in addition to, and with greater affinity than, H1.
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology*; D006919:Hydroxyzine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology*; D014132:Trachea / Q000502:physiology
chemical_list: D006633:Histamine Antagonists; D010714:Phosphatidylethanolamines; D013629:Tamoxifen; C016601:afimoxifene; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; D006919:Hydroxyzine; D012701:Serotonin; D006632:Histamine; D011738:Pyrilamine; D000109:Acetylcholine; D011188:Potassium