Synthesis and pharmacological activity of fluorescent histamine H1 receptor antagonists related to mepyramine

Fluorescently labeled histamine H1 receptor antagonists were synthesized starting from N-demethylmepyramine by introduction of ω-aminoalkyl chains (2–8 methylene groups in length) followed by derivatization of the terminal NH2 group with various fluorophores (fluorescein, naphthofluorescein, rhodamine, tetramethylrhodamine, BODIPY, dansyl, and nitrobenzoxadiazole (NBD)). On the isolated guinea pig ileum and in a Ca2+ assay on U373MG human glioblastoma cells the highest H1 antagonistic activities were found in 5- and 6-carboxyfluorescein labeled compounds with hexa- and octamethylene spacers and in an analogous NBD-aminohexanoyl derivative (pA2 or pKB values in the range: 8.3–9.0; compared to 9.3–9.4 for mepyramine).