Comparative Studies on Anti-Nicotinic Action of Hexamethonium, Mecamylamine and Adenosine in the Guinea Pig Isolated Ileum

Abstract

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 mecamyl amine does not appear to he 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.Stone et al. (1) found that a secondary amine, 3-methylaminoisocamphane hydro chloride (mecamylamine) had a potent ganglion-blocking action with a long duration and suggested the similarity of its action to a quarternary ammonium ion, hexamethonium. On the other hand, Bennet et al. (2) reported that the mode of action of mecamylamine completely differed from that of hexamethonium and pentolinium in that mecamylamine, a substance readily diffusible into cells, was not competitive with acetylcholine at the auto nomic ganglia and neuromuscular junction. In the guinea pig isolated intestine, mecamyla mine reportedly exerts non-competitively or competitively-non-competitive antagonism on the dose-response curves for nicotinic stimulants (3-6).Adenosine, a potent coronary vasodilator, reduces acetylcholine release from post ganglionic nerves and exerts an anti-nicotinic action (7-10). However, the mechanism by which mecamylamine and adenosine show anti-nicotinic action has not been fully characterized.In an attempt to determine the mechanism of the anti-nicotinic action, effects on the contractile responses of the guinea pig isolated ileum to agonists such as nicotine, acetyl choline and 5-hydroxytryptamine, and to transmural stimulation were examined using hexamethonium as the reference compound.

The role of prostacyclin in modulating cholinergic neurotransmission in guinea‐pig ileum

“…There are, however, species and regional differences in the parasympathetic blocking action of this toxin, guinea-pig ileum being only partially sensitive to it (Miura et al, 1981). This would agree with the fact that, in our experiments, P-bungarotoxin reduced, but did not abolish the contractions elicited by PGI2-The ganglionic blocker hexamethonium has been shown to act as a competititive antagonist on nicotinic receptors in guinea-pig ileum, without affecting transmitter release (Hayashi, Yamada & Mori, 1977).…”

Effects of Adenosine on Contractile Response of Circular Muscle in Electrically Stimulated Guinea-Pig Ileum

“…In the ileal longitudinal muscle, it is generally accepted that contraction induced by single low-frequency stimuli is a cholinergic response (9). In the previous report, we had shown that adenosine and its related com pounds depressed the electrically-induced twitch response of the ileal longitudinal muscle of guinea-pigs (1), and the present study showed that adenosine depressed the electrically-induced twitch response of the circular muscle, concentration-dependently.…”

Proceedings of the Australasian Society of Clinical and Experimental Pharmacologists

“…The EDSO for inhibition of nicotine responses or responses to submaximal transmural stimulation was 1.1 pmol/l. The inhibition of nerve-mediated contractions appeared to be due to inhibition of transmitter release from nerve endings in the ileum, as has been suggested for the action of adenosine (Sawynok & Jhamandas, 1976, Hayashi et al, 1977. Theophylline antagonized the action of I-methylisoguanosine and overall the results suggest that 1 -methylisoguanosine acts at an adenosine receptor in the guinea-pig ileum, but is approximately ten times more potent than adenosine itself.…”