Comparative studies on anti-nicotinic action of hexamethonium, mecamylamine and adenosine in the guinea pig isolated ileum.

The mechanism of anti-nicotinic actions of hexamethonium, mecamylamine and adenosine was investigated in guinea pig isolated ileum. Mecamylamine shifted the dose-response curves for nicotine to the right with a gradual depression. On the other hand, hexamethonium shifted the curves to the right without a depression and adenosine made only a gradual depression, suggesting the different modes of their antinicotinic actions. The transmurally-stimulated twitch response was unaffected, partially inhibited and abolis hed by hexamethonium, mecamylamine and adenosine, respectively. These three compounds also had little effect on direct muscle response to acetylcholine and on the acetylcholinesterase activity of the ileum. From these results, it is suggested that the antagonism to the effect of nicotine shown by mecamylamine does not appear to be a simple competitive blockade of ganglionic receptors as is the case with hexamethonium and that adenosine may antagonize the effect of nicotine non-competitively. The mechanism by which mecamylamine and adenosine showed anti-nicotinic action is discussed.