title: Synthesis and pharmacological activity of fluorescent histamine H1 receptor antagonists related to mepyramine.
abstract: Fluorescently labeled histamine H(1) receptor antagonists were synthesized starting from N-demethylmepyramine by introduction of omega-aminoalkyl chains (2-8 methylene groups in length) followed by derivatization of the terminal NH(2) group with various fluorophores (fluorescein, naphthofluorescein, rhodamine, tetramethylrhodamine, BODIPY, dansyl, and nitrobenzoxadiazole (NBD)). On the isolated guinea pig ileum and in a Ca(2+) assay on U373MG human glioblastoma cells the highest H(1) antagonistic activities were found in 5- and 6-carboxyfluorescein labeled compounds with hexa- and octamethylene spacers and in an analogous NBD-aminohexanoyl derivative (pA(2) or pK(B) values in the range: 8.3-9.0; compared to 9.3-9.4 for mepyramine).
authors.affiliation: College of Pharmaceutical Sciences, Peking University, PR, China.
authors.forename: Liantao
authors.initials: L
authors.lastname: Li
authors.forename: Julia
authors.initials: J
authors.lastname: Kracht
authors.forename: Shiqi
authors.initials: S
authors.lastname: Peng
authors.forename: Günther
authors.initials: G
authors.lastname: Bernhardt
authors.forename: Armin
authors.initials: A
authors.lastname: Buschauer
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000494:pharmacology*; D016257:Fura-2 / Q000031:analogs & derivatives* / Q000737:chemistry; D005909:Glioblastoma / Q000378:metabolism; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D011738:Pyrilamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D014407:Tumor Cells, Cultured
chemical_list: D005456:Fluorescent Dyes; D006634:Histamine H1 Antagonists; D007202:Indicators and Reagents; C049925:fura-2-am; D011738:Pyrilamine; D016257:Fura-2