THE EXCITATORY EFFECT OF THE NEW HISTAMINE H_2-RECEPTOR ANTAGONIST NIZATIDINE (LY 139037) ON THE GUINEA PIG ILEUM

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The histamine H_2-receptor antagonist, nizatidine (LY 139037), was tested for its effect on the intestinal smooth muscle. 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) caused a concentration-dependent contractile response by the guinea pig ileum. The average maximum response to nizatidine (3.2×10^<-4>M) was about 89% of the average maximum response to eserine (3.2×10^<-6>M). The contractile responses induced by nizatidine were not modified by pyrilamine (10^<-8> and 10^<-7>M). On the other hand, atropine (10^<-8> and 3.2×10^<-8>M) significantly prevented, while eserine (10^<-8> and 3.2×10^<-8>M) significantly enhanced the nizatidine-induced responses in a concentration-dependent manner. These findings suggest that nizatidine exerts an excitatory effect on the guinea pig ileum which seems to be associated with the cholinergic system, probably through a direct and/or an indirect mechanism (inhibition of acetylcholinesterase and/or increased release of acetylcholine).
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