Nizatidine enhances the gastrocolonic response and the colonic peristaltic reflex in humans

Animal studies demonstrate that nizatidine, an H2-receptor inhibitor, may enhance colonic activity independent of its effect on acid secretion. The effect of nizatidine on human colonic motility is unknown. We evaluated the potential prokinetic property of nizatidine in 12 healthy subjects (10 men and 2 women, age 21-46 years). Each subject received either nizatidine (600 mg), famotidine (80 mg, a H2-receptor inhibitor used as a control), or a placebo, on separate days in randomized order at least 3 days apart. Following an overnight fast, a three-lumen catheter fitted with a stimulus balloon and two barostat bags was placed in the descending colon. The gastrocolonic response was tested by antral balloon inflation and the colonic peristaltic reflex was evaluated by colonic distension. Changes in colonic motility were assessed by volume changes in the barostat bags. Antral distension evoked volume-dependent increases in colonic motility, maximal at a 300-ml inflation, as demonstrated by a reduced bag volume. Nizatidine enhanced colonic motility in response to antral distension at 200 and 300 ml, compared with famotidine and placebo. Colonic distension evoked volume-dependent increases in colonic motility proximal to the stimulus balloon. Compared with famotidine and placebo, nizatidine enhanced the ascending and descending contractile limbs of the peristaltic reflex but did not affect relaxation distal to the balloon. In conclusion, nizatidine enhanced the gastrocolonic response and the colonic peristaltic reflex in healthy subjects. Further research on the prokinetic action of nizatidine in the colon may lead to novel treatments for idiopathic constipation.