The excitatory effect of the new hstamine H2-receptor antagonist nizatidine (LY 139037) on the guinea pig ileum.

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Abstract
The histamine H2-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.degree. C. Nizatidine (from 3.2 .times. 10-6 to 3.2 .times. 10-4 M) caused a concentration-dependent contractile response by the guinea pig ileum. The average maximum response to nizatidine (3.2 .times. 10-4 M) was about 89% of the average maximum response to eserine (3.2 .times. 10-6 M). The contractile responses induced by nizatidine were nor modified by pyrilamine (10-8 and 10-7 M). On the other hand atropine (10-8 and 3.2 .times. 10-8 M) significantly prevented, while eserine (10-8 and 3.2 .times. 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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