Abstract
A series of tertiary amines structurally related to the potent muscarinic agent oxotremorine showed weak stimulant activity on the frog rectus abdominis preparation. The corresponding quaternary ammonium salts were more effective stimulants, the most potent being half as active as carbachol. The effects appeared to be due to direct stimulation of post-junctional nicotinic receptors. The relationship between the structures of these compounds and their ability to stimulate nicotinic receptors was compared with the structure-activity relationships in more conventional nicotinic stimulants. Finally, a comparison was made between the observed nicotinic potencies and previously published muscarinic potencies in the isolated guinea pig ileum. The tertiary amines were in general highly selective for muscarinic as opposed to nicotinic receptors, whereas the quaternary derivatives were only slightly more selective for muscarinic receptors than carbachol.
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