Nonclassical nicotine antagonists.
A series of "nonclassical" nicotine antagonists was synthesized and compared to the "classical" nicotine antagonist, hexamethonium, by means of the isolated guinea pig atria preparation. 2 was found to be the most potent, followed by hexamethonium and the other antagonists. With the exception of 5, the bisquaternary compounds 1-3 and 7-9 were found to be more potent than the monoquaternary compounds 4, 6, and 10-12. Within a series of compounds (1-6 or 7-12), those compounds possessing two phenyl rings proved to be more potent than those possessing one or three phenyl rings. These and other aspects of the structure-activity relationship of this class of compounds are discussed.
D000818:Animals; D005730:Ganglionic Blockers / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013730:Terphenyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology
D005730:Ganglionic Blockers; D000644:Quaternary Ammonium Compounds; D013730:Terphenyl Compounds