mdl-100907 and Dyspepsia

Functional dyspepsia is a highly common disorder. The physiopathological mechanisms of this entity are not yet completely known and prokinetic drugs seem to be useful. The aim of this study was to evaluate the prokinetic effect of cinitapride in patients with dysmotility-like dyspepsia and delayed gastric emptying.. Nineteen patients were randomized to receive 1mg of an oral solution of cinitapride t.i.d or placebo for 4 weeks in two consecutive periods, following a crossover and double-blind design. The main variable was the mean change from baseline after 4 weeks of treatment in gastric-emptying half-time after a liquid test meal, measured by real-time ultrasonography.. At the end of treatment, the mean gastric-emptying half-time decreased with both treatments, with no statistically significant differences between them (ANOVA, p=0.8720). This decrease was greater for cinitapride than for placebo (ANOVA, p=0.0169) in patients with mild-to-moderate delayed gastric emptying. In this group of patients, cinitapride was also superior to placebo in the percentage AUC of the antral area and the percentage of days free of nausea. Cinitapride was well tolerated, with a safety profile comparable to that of placebo.. Oral cinitapride is safe and effective in improving gastric emptying and symptoms in patients with dysmotility-like dyspepsia and mild-to-moderate delayed gastric emptying.

Topics: Adult; Aged; Benzamides; Computer Systems; Cross-Over Studies; Dopamine D2 Receptor Antagonists; Double-Blind Method; Dyspepsia; Electrocardiography; Female; Gastric Emptying; Gastroparesis; Humans; Male; Middle Aged; Pyloric Antrum; Serotonin 5-HT2 Receptor Antagonists; Serotonin 5-HT4 Receptor Agonists; Serotonin Agents; Ultrasonography; Young Adult

Psychological stress has been shown to impair gastric accommodation (GA), but its mechanism has not been elucidated. This study was conducted to clarify the role of 5-HT2B receptors in a guinea pig model of stress-induced impairment of GA.. Gastric accommodation was evaluated by measuring the intrabag pressure in the proximal stomach after administration of a liquid meal. The guinea pigs were subjected to water-avoidance stress. The role of 5-HT2B receptors in impairment of GA was investigated by administering a 5-HT2B receptor agonist (BW723C86) or antagonist (SB215505), the traditional Japanese medicine rikkunshito (RKT), a muscarinic M3 receptor antagonist (1,1-dimethyl-4-diphenylacetoxypiperidium iodide [4-DAMP]), or a nitric oxide synthase inhibitor (Nω -nitro-L-arginine [L-NNA]).. In normal animals, liquid meal-induced GA was inhibited by BW723C86, but was not affected by SB215505. The inhibition of GA by BW723C86 was reversed by co-administration of 4-DAMP. Compared to normal animals, GA in stressed animals was significantly inhibited. SB215505 and RKT significantly suppressed stress-induced impairment of GA. After meal administration, the level of cyclic guanosine monophosphate in gastric fundus tissue increased by approximately twofold in normal animals, but did not change in stressed animals. The inhibition of GA by L-NNA was suppressed by SB215505 or RKT. At a dose that did not affect GA in normal animals, BW723C86 exacerbated the impairment of GA in stressed animals.. Stress-induced impairment of GA may be mediated by an increased responsiveness of 5-HT2B receptors, and activation of the 5-HT2B receptor signaling pathway may have an inhibitory effect on nitric oxide function.

Topics: Animals; Avoidance Learning; Dyspepsia; Gastric Fundus; Gastric Mucosa; Guinea Pigs; Male; Nitric Oxide; Receptor, Serotonin, 5-HT2B; Serotonin 5-HT2 Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Stress, Psychological; Water

Topics: Arrhythmias, Cardiac; Aryl Hydrocarbon Hydroxylases; Benzamides; Cisapride; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP3A; Drug Interactions; Dyspepsia; Electrocardiography; Gastrointestinal Agents; Humans; Ketoconazole; Serotonin 5-HT2 Receptor Antagonists; Serotonin 5-HT4 Receptor Agonists