Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Functional gastrointestinal disorders are characterised by central and peripheral physiological changes, associated with psychological factors. Successful drug development has been hindered by lack of adequate characterisation of the nature of symptoms and their physiological and psychological correlates. Animal models of chronic stress are lacking. High levels of drug safety are now demanded for treating non-life threatening conditions. Once close to market, patient pressure groups, health care providers and insurers, government, and the internet can all influence a drug's success. Serotonin-modifying drugs have been the main recent focus of development, with mixed results. Cisapride has been withdrawn because of concerns related to QT prolongation and cardiac arrhythmias. The 5-HT3 antagonists have been developed on the questionable assumption that they modify visceral sensation in patients. Problems have arisen with alosetron being associated with ischaemic colitis and a high incidence of constipation. The 5-HT4 agonists have their major effect on inducing peristalsis, and may modify gut secretion and sensory function. Tegaserod and prucalopride show promise in patients with constipation and related symptoms. 5-HT1 agonists may play a role in treating functional dyspepsia, partly by improving impaired gastric accommodation to a meal. Antidepressants, often found to be clinically beneficial in these disorders, also affect serotonin metabolism. Past successes, such as loperamide or the somatostatin analogue octreotide, involved targeting end organ receptors influencing motor function or secretion. Modifying sensory function is much more challenging. Future research with novel compounds need to keep these recent lessons in mind.
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PMID:Pharmacological treatment of irritable bowel syndrome--from concept to sales. 1614 96

The gastrointestinal transit can be disturbed in different situations by increased or decreased motility patterns. Pharmacological treatment of gastrointestinal motility disorders is intended to inhibit or stimulate motility. Prokinetic agents as metoclopramide, domperidone, erythromycin or tegaserod are used in clinical settings. We discuss their use in functional dyspepsia and gastroparesis. Management of chronic constipation consists of increasing fluid and dietary fiber intake and increasing physical activity. Fiber, lubricants, osmotic and stimulative laxatives increase stool frequency and improve symptoms of constipation. Treatment of irritable bowel syndrome (IBS) should focuses on the specific gastrointestinal complaints. In constipation predominant IBS fiber and isoosmotic laxatives are used first line. Tegaserod has an advantage over placebo in constipation-predominant IBS. Pain can be treated with antispasmodic agents and tricyclic antidepressants in low doses. The diarrhea-predominant IBS responds well to a loperamide treatment.
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PMID:[Pharmacologic treatments of transit disorders]. 1766 10

BACKGROUND Tegaserod, a serotonin receptor type-4 partial agonist, stimulates gastrointestinal motility and has been shown to increase gastric volumes before and after a meal in healthy volunteers. Its effect on gastric motor and sensory function in patients with functional dyspepsia is unclear. AIM To evaluate the effects of tegaserod on gastric compliance, accommodation and gastric sensory function in patients with functional dyspepsia and healthy volunteers. METHODS Sixteen patients with functional dyspepsia and 12 healthy volunteers were studied on two occasions, each after a 7-day treatment with either placebo or tegaserod 6 mg b.d. using a double-blind, randomized, crossover design. After each treatment period a gastric barostat study was performed fasting and during intraduodenal lipid infusion. RESULTS Tegaserod increased postprandial gastric compliance in functional dyspepsia patients (P = 0.04). Healthy volunteers showed enhanced postprandial gastric compliance after placebo (P = 0.03). Between-treatment analysis of gastric accommodation revealed a significant increase in intrabag volumes after tegaserod in healthy volunteer (P = 0.04); no difference could be seen in functional dyspepsia patients. Tegaserod had no effect on gastric sensation. CONCLUSIONS Tegaserod enhances postprandial gastric compliance in functional dyspepsia patients and gastric accommodation in healthy volunteers. The improvement of proximal gastric motor function suggests a beneficial role of tegaserod in patients with functional dyspepsia.
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PMID:Clinical trial: effects of tegaserod on gastric motor and sensory function in patients with functional dyspepsia. 1789 26

BACKGROUND AND AIMS: Tegaserod is a selective serotonin receptor (5-HT(4)) agonist that relieves dysmotility symptoms associated with constipation. Here we explore its effects on functional dyspepsia symptoms and heartburn during continued proton pump inhibitor (PPI) treatment. METHODS: In this multicenter pilot study, following a 2-week screening/baseline period, women with functional dyspepsia and persisting heartburn treated with PPIs received add-on open-label tegaserod 6 mg twice daily (bid) for 4 weeks. Treatment responders were then randomized 1:1 to continue double-blind tegaserod or placebo therapy for 6 weeks. Efficacy variables included the proportion of days with satisfactory relief of dyspepsia symptoms (early satiety, postprandial fullness and bloating) as well as the change in individual symptom severity scores for these three cardinal dyspepsia symptoms. Health-related quality of life was evaluated using a validated questionnaire, the Nepean Dyspepsia Index. Adverse events (AEs) were monitored. RESULTS: Of 101 women enrolled, 71 completed open-label treatment, and 70 responders were randomized to double-blind treatment. The proportion of days with satisfactory relief of dyspepsia symptoms (least squares mean, LSM) increased with tegaserod and placebo, to 0.69 and 0.62, respectively at study end (P = 0.366). Similarly, both groups showed improvements in the composite daily symptom severity score (overall LSM change from baseline of 1.55 and 1.57, P = 0.934), and the Nepean Dyspepsia Index (overall LSM change of -39.0 and -37.8, P = 0.537). Tegaserod was well tolerated. Diarrhea was the most common AE (8.1% tegaserod, 0% placebo). There were no serious AEs or deaths. CONCLUSIONS: A significant treatment effect was not demonstrated in this study using a treatment-withdrawal methodology. In future studies of functional dyspepsia patients with heartburn, a more rigorous parallel-group study design should be considered.
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PMID:Exploratory Study of Tegaserod for Dyspepsia in Women Receiving PPIs for Heartburn. 1963 28