Synthesis and biological characterization of pyridohomotropanes. Structure-activity relationships of conformationally restricted nicotinoids

Abstract

The recently discovered nicotinic agonist pyrido[3,4-b]homotropane (PHT) as well as its N-methyl and 2''-methyl derivatives (syntheses reported herein) were compared with nicotine, nornicotine, and anatoxin .alpha. in a series of in vitro and in vivo [rat and Torpedo] assays. The results reveal that PHT possesses activity comparable to that of the highly potent agonist, anatoxin .alpha.. The inactivity observed relative to PHT of N-methyl- and 2''-methyl-PHT has helped to further define the structure-activity requirements of conformationally restricted nicotinoids.