Synthesis and pharmacological activity of fluorescent histamine H1 receptor antagonists related to mepyramine.
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).
Li
Liantao
L
College of Pharmaceutical Sciences, Peking University, PR, China.
Kracht
Julia
J
Peng
Shiqi
S
Bernhardt
Günther
G
Buschauer
Armin
A
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
D005456:Fluorescent Dyes; D006634:Histamine H1 Antagonists; D007202:Indicators and Reagents; C049925:fura-2-am; D011738:Pyrilamine; D016257:Fura-2