Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1291077 (bloating)
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Tegaserod is a medication that has been shown to be of benefit in women with irritable bowel syndrome (IBS) associated with abdominal pain, bloating, and constipation. Tegaserod is a selective serotonin receptor subtype 4 partial agonist designed to interact with the network of cells and nerves throughout the gastrointestinal tract that use serotonin. Tegaserod has been shown to modulate both gastrointestinal motility and visceral sensitivity. Specifically, it increases the peristaltic reflex and decreases visceral sensitivity. Clinical studies have shown that tegaserod improves symptoms of abdominal pain, bloating, and constipation in women with IBS. This article discusses the role of serotonin in gastrointestinal tract physiology, the structure and pharmacokinetic profile of tegaserod, and clinical applications of this new drug.
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PMID:Tegaserod: a new 5-HT4 agonist. 1174 42

Irritable bowel syndrome (IBS) is a common functional bowel disorder of unknown aetiology. It is defined by the presence of gastrointestinal (GI) symptoms including abdominal pain/discomfort, bloating and bowel motor dysfunction. No available therapy is yet effective against all the symptoms of the disorder. Current treatments therefore target individual symptoms but may be accompanied by unpleasant side-effects. Tegaserod is a novel selective serotonin receptor type-4 (5-HT4) partial agonist with structural similarity to 5-HT Tegaserod stimulates small bowel and colonic motility and helps to normalise GI function. Clinical trials using a patient's assessment of efficacy demonstrate that tegaserod significantly improves key symptoms of IBS: abdominal pain/discomfort, bloating and constipation. Tegaserod is well tolerated with an excellent safety profile and represents a significant treatment advance in this difficult-to-treat disorder.
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PMID:Tegaserod: a novel, selective 5-HT4 receptor partial agonist for irritable bowel syndrome. 1183 35

Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder affecting up to 3-15% of the general population in Western countries. It is characterised by unexplained abdominal pain, discomfort and bloating in association with altered bowel habits. The pathophysiology of IBS is considered to be multifactorial, involving disturbances of the brain-gut-axis: IBS has been associated with abnormal gastrointestinal motor functions, visceral hypersensitivity, psychosocial factors, autonomic dysfunction and mucosal inflammation. Traditional IBS therapy is mainly symptom oriented and often unsatisfactory. Hence, there is a need for new treatment strategies. Increasing knowledge of brain-gut physiology, mechanisms, and neurotransmitters and receptors involved in gastrointestinal motor and sensory function have led to the development of several new therapeutic approaches. This article provides a systematic overview of recently approved or novel medications that show promise for the treatment of IBS; classification is based on the physiological systems targeted by the medication. The article includes agents acting on the serotonin receptor or serotonin transporter system, novel selective anticholinergics, alpha-adrenergic agonists, opioid agents, cholecystokinin antagonists, neurokinin antagonists, somatostatin receptor agonists, neurotrophin-3, corticotropin releasing factor antagonists, chloride channel activators, guanylate cyclase-c agonists, melatonin and atypical benzodiazepines. Finally, the role of probiotics and antibacterials in the treatment of IBS is summarised.
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PMID:Irritable bowel syndrome: recent and novel therapeutic approaches. 1678 93

Gastroparesis is a disorder of gastric emptying that occurs in the absence of mechanical obstruction. Its cardinal features include nausea, vomiting, bloating, early satiety and discomfort. Weight loss, dehydration, electrolyte disturbances and malnutrition may develop in severe cases. The majority of cases is idiopathic, long standing diabetes mellitus is responsible for about 25-30% of cases. Diabetic gastroparesis may render glucose control extremely difficult, its treatment represents a major challenge. Besides frequent, small meals and psychological support, several drug options are available, however, their efficacy is limited and only a few randomized studies have been performed to date. Prokinetic agents (erythromycin, domperidone, metoclopramide) and antiemetics (phenothiazines, serotonin antagonists, butyrophenones) are the most wide-spread medicaments. Among the novel, recently developed agents, 5-HT4 serotonin receptor agonists and dopamine D2 receptor antagonists are the most promising. Injection of botulinum toxin into the pyloric sphincter resulted in faster gastric emptying and symptom alleviation in some studies. Gastric electric stimulation appears to be one of the most effective options, both low and high-frequency stimulation may alleviate symptoms. Gastrostomy/jejunostomy and other surgical interventions are considered as "last resort".
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PMID:[Gastroparesis and its treatment options]. 1829 33

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

Irritable bowel syndrome is a functional gastrointestinal disorder affecting up to 3-15% of the general population in western countries. It is characterised by unexplained abdominal pain, discomfort, and bloating in association with altered bowel habits. The pathophysiology of irritable bowel syndrome is multifactorial involving disturbances of the brain-gut axis. The pathophysiology provides the rationale for pharmacotherapy: abnormal gastrointestinal motor functions, visceral hypersensitivity, psychosocial factors, autonomic dysfunction, and mucosal immune activation. Understanding the mechanisms, and their mediators or modulators including neurotransmitters and receptors have led to several therapeutic approaches including agents acting on the serotonin receptor or serotonin transporter system, antidepressants, novel selective anticholinergics, alpha-adrenergic agonists, opioid agents, cholecystokinin-antagonists, neurokinin-antagonists, somatostatin receptor agonists, corticotropin releasing factor antagonists, chloride channel activators, guanylate cyclase-c agonists, melatonin, atypical benzodiazepines, antibiotics, immune modulators and probiotics. The mechanisms and current evidence regarding efficacy of these agents are reviewed.
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PMID:Current and novel therapeutic options for irritable bowel syndrome management. 1966 53

Tegaserod, a novel serotonin receptor agonist, has gained acceptance and widespread use for the treatment of women with irritable bowel syndrome and constipation. Development of this therapy evolved from the emerging role of serotonin in gastrointestinal motor, secretory and sensory functions. The efficacy and safety of tegaserod has been well established in women suffering from irritable bowel syndrome with constipation. Large, randomized, double-blind, placebo-controlled trials involving more than 3500 predominantly female patients with irritable bowel syndrome and constipation have demonstrated the superiority of tegaserod over placebo in improving global and individual symptoms. The most common side effects of tegaserod in clinical trials were diarrhea and headache. Recent data suggest that retreatment with tegaserod after a drug holiday is efficacious, opening the door to the possibility of intermittent therapy for patients with irritable bowel syndrome and constipation. Areas in need of further investigation include the role of tegaserod in the treatment of pain and bloating in irritable bowel syndrome, whether tegaserod has a role in male patients, the long-term efficacy of tegaserod, whether tolerance develops in a subset of patients with extended therapy and whether tegaserod is beneficial for the treatment of other functional gastrointestinal disorders.
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PMID:Tegaserod in the treatment of irritable bowel syndrome with constipation. 1980 24