Synthesis and pharmacological activity of fluorescent histamine H2 receptor antagonists related to potentidine.

Fluorescently labeled histamine H(2) receptor antagonists were synthesized starting from N-cyano-N'-[3-(3-piperidin-1-ylmethylphenoxy)propyl]guanidines with an additional N"-omega-aminoalkyl substituent (chain lengths 2-8 methylene groups) or from 3-(3-piperidin-1-ylmethylphenoxy)propylamine. The primary amino group was derivatized with various fluorophores (fluorescein, acridine, dansyl, nitrobenzoxadiazole (NBD), indolo[2,3-a]quinolizine). On the isolated spontaneously beating guinea pig right atrium most of the fluorescent probes were only weakly active, however, the NBD-labeled substances proved to be potent histamine H(2) receptor antagonists achieving pA(2) values in the range of 7.5-8.0, comparable to the activity of famotidine.