Inhibition of Acetylcholinesterase by the H_2-Receptor Antagonist Nizatidine

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The purpose of the present investigation was to study if the stimulating effect of nizatidine on the intestinal smooth muscle is related to the acetylcholinesterase activity. Isolated segments of guinea pig ileum were used in Tyrode solution at 37℃. Nizatidine (from 3.2×10^<-6> to 3.2×10^<-4>M) exerted a concentration-dependent contractile effect on the guinea pig ileum. The average maximum activity (mean±S.E.M.) of nizatidine (3.2×10^<-4>M) was 96.21±6.19% of the average maximum activity of neostigmine (3.2×10^<-6>M). The acetylcholine-induced contractions (from 10^<-8> to 3.2×10^<-6>M) were augmented by nizatidine (from 10^<-5> to 10^<-4>M) in a similar way to that by neostigmine (from 10^<-8> to 10^<-7>M). The acetylcholine-induced contractions were prevented by acetylcholinesterase (0.1 unit/ml). This acetylcholinesterase activity was inhibited by nizatidine (from 10^<-5> to 10^<-4>M) and this inhibition was similar to that of neostigmine (from 10^<-8> to 10^<-7>M). These findings suggest that the stimulating effect of nizatidine on the intestinal smooth muscle of the guinea pig ileum could be explained by the inhibition of acetylcholinesterase activity.
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