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)

Temporary electrodes implanted under general anaesthesia, or via an oral or percutaneous endoscopic gastrostomy route have been used for testing of gastric electrical stimulation (GES). We have developed a principle for percutaneous electrode implantation. Leads were constructed so that the tip could be anchored to the gastric submucosa under gastroscopic control. Acute experiments were performed in anaesthetized pigs. Three patients referred for nausea and/or vomiting and non-established indications for GES (chronic intestinal pseudo-obstruction, functional dyspepsia without gastroparesis) were evaluated. Electrode function was tested by recording and stimulation techniques. In the pigs, a slow-wave (SW) rhythm (3 min(-1)) was recorded with decrease in frequency at the end of the experiments. In the patients, implantation time from start of gastroscopy to end of electrode placement was 12-20 min. Electrode distance varied from 12 to 45 mm. Gastric electromyography showed a regular SW rhythm of about 3 min(-1). Antral pressure waves had intervals being multiples of the SW-to-SW time. With temporary GES for 7-9 days, weekly frequency of the referral symptoms decreased >80% in two patients and 33% in one patient. Temporary percutaneous gastric leads can easily be implanted and may be used for testing of GES and study of gastric electrophysiology.
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PMID:Percutaneous implantation of gastric electrodes - a novel technique applied in animals and in patients. 1724 64

The effects of mitemcinal (GM-611) on the gastrointestinal contractile activity were investigated using chronically implanted force transducers in conscious dogs and were compared with the effects of porcine motilin (pMTL), EM-523 and EM-574. In the interdigestive state, intravenous and oral administration of mitemcinal, EM-523 and EM-574 induced the gastrointestinal contractile activity in a manner similar to pMTL. The contractile activity caused by mitemcinal was suppressed by continuous intravenous infusion of a motilin receptor antagonist. In the digestive state, intravenous and oral administration of mitemcinal, EM-523 and EM-574 also stimulated the gastrointestinal contractile activity. Mitemcinal, EM-523 and EM-574 given intravenously increased the gastric contractile activity in a similar dose range; however, mitemcinal was approximately 10 times more potent than EM-523 and EM-574 when administered orally in the digestive state. These results indicate that the mitemcinal-induced gastrointestinal contractile activity operates via motilin receptors and possesses a higher activity than EM-523 and EM-574 when administered orally in conscious dogs in the digestive state. Mitemcinal may therefore be useful in the treatment of several gastrointestinal disorders involving dysmotility, such as gastroparesis and functional dyspepsia, even when administered orally.
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PMID:Effects of mitemcinal (GM-611), an acid-resistant nonpeptide motilin receptor agonist, on the gastrointestinal contractile activity in conscious dogs. 1742 10

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

We assessed and compared the effects of oral mitemcinal (an orally active, erythromycin-derived motilin-receptor agonist; Code name: GM-611), erythromycin, EM-574 and cisapride on gastric emptying in conscious Rhesus monkeys using the acetaminophen method. Mitemcinal and erythromycin induced significant, dose-dependent increases in indices of gastric emptying, but mitemcinal required a much lower dose for the same effect. Cisapride induced a bell-shaped dose response, and EM-574, a potent erythromycin derivative and originally developed as an enteric coated formulation, had little effect when it was given orally uncoated. Since our previous study showed that response to motilin is similar in Rhesus monkeys and humans, these results suggest that oral mitemcinal may be effective for the treatment of symptoms in human disorders related to delayed gastric emptying (e.g., functional dyspepsia and gastroparesis). Combined with the results of other studies, these results suggest that mitemcinal may be able to replace the withdrawn drug, cisapride, as the drug of choice for treating delayed gastric emptying.
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PMID:Effects of oral mitemcinal (GM-611), erythromycin, EM-574 and cisapride on gastric emptying in conscious rhesus monkeys. 1793 42

Functional diseases of the stomach include visceral hypersensitivity, gastric dysrhythmias, dysfunction of gastric fundus and acommodation, functional diseases of antrum and gastroparesis. A common symptom of this diseases is dyspepsia. A background of dyspepsia state functional and organic abnormalities of upper gastrointestinal tract. The most serious abnormality is gastroparesis. In this review we provide an overview of functional gastroparesis focusing on postoperative and hormonal related gastric dysfunction.
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PMID:[Pathomechanisms of functional gastroparesis]. 1803 12

The concept of the gut forming the centre of an integrated gut-brain-energy axis - modulating appetite, metabolism and digestion - opens up new paradigms for drugs that can tackle multiple symptoms in complex upper gastrointestinal disorders. These include eating disorders, nausea and vomiting, gastroesophageal reflux disease, gastroparesis, dyspepsia and irritable bowel syndrome. The hormones that modulate gastric motility represent targets for gastric prokinetic drugs, and peptides that modify eating behaviours may be targeted to develop drugs that reduce nausea, a currently poorly treated condition. The gut-brain axis may therefore provide a range of therapeutic opportunities that deliver a more holistic treatment of upper gastrointestinal disorders.
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PMID:Hormones of the gut-brain axis as targets for the treatment of upper gastrointestinal disorders. 1830 13

Mosapride was effective in improving overall symptoms in patients with gastrointestinal disorders, including chronic gastritis, gastro-oesophageal reflux disease and functional dyspepsia. Mosapride was more effective than teprenone in improving gastric stasis symptoms and gastric pain after 2 weeks of therapy (p < 0.001) in an open-label trial in 1042 patients with functional dyspepsia. Mosapride was as effective as famotidine and itopride, but more effective than tandospirone, in improving overall or individual symptoms of functional dyspepsia in randomized trials. However, in one randomized, double-blind trial in patients with mild to severe disease, the improvement in overall symptoms of functional dyspepsia did not differ significantly between mosapride or placebo treatment. Mosapride was well tolerated, with diarrhoea/loose stools, dry mouth, malaise and headache being reported in <5% of patients.
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PMID:Mosapride in gastrointestinal disorders. 1845 63

Many patients with diabetes mellitus suffer from upper and lower GI symptoms. The reported prevalence of these symptoms varies among different ethnic groups/populations. The natural history of GI symptoms as well as their pathogenesis in patients with diabetes remains poorly understood, although it is known that gastric emptying is influenced by hyperglycemia, euglycemia, and hypoglycemia. Poor glycemic control over a long period of time can lead to neuropathy and damage the vagus nerve, resulting in diabetic gastroparesis whose signs and symptoms vary in the individual patient. Gastroparesis can further worsen glycemic control by adversely altering the pharmacokinetics of orally administered hypoglycemic agents as well as by altering the delivery of diet-derived calories to intestines from which absorption, subsequently, determines incipient blood glucose, and thus effectiveness of various injectable antidiabetics including various insulins and related insulin analogs. As GI symptoms may overlap with other disorders, including functional dyspepsia, irritable bowel syndrome, and depression, it is important to have such patients/patients with diabetes undergo standardized testing for measuring gastric emptying. Certain medications including metformin, amylin analogues (i.e. pramlintide), glucagon-like peptide 1 analogs (i.e. exenatide, liraglutide), anticholinergic agents, antidepressants, calcium-channel blockers, and others may contribute to GI symptoms observed in patients with diabetes. Given the global diabetes pandemic, it is of utmost importance to not only diagnose and treat present patients with diabetes mellitus and its comorbidities, but also to help prevent the development of further disease burden by educating children and adolescents about healthy lifestyle modifications (avoidance of overeating, portion control, healthy food choices, increased physical and reduced sedentary activity), as changing behavior in adulthood has proven to be notoriously difficult.
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PMID:Are gastrointestinal symptoms related to diabetes mellitus and glycemic control? 1879 3

Gastrointestinal prokinetics are a heterogeneous class of drugs that stimulate smooth muscle contractions to enhance gastric emptying and intestinal transit. Recently studied prokinetics include antidopaminergic agents (itopride), serotonergic agents (tegaserod and others), and motilin receptor agonists and ghrelin receptor agonists (mitemcinal, TZP101). It has been difficult to establish symptomatic benefit with prokinetic drugs in gastroparesis and functional dyspepsia, because of pathophysiological heterogeneity of the patient populations, a lack of well-accepted endpoints, and inconsistent relationships between changes in motor function and symptomatic outcome. Fundic relaxant drugs are a recent different approach to treatment of gastric motility disorders. Recently studied drugs include drugs under investigation including nitrates, serotonin reuptake blockers, 5-HT(1A) receptor agonists (buspirone and R137696), and muscarinc M1/M2 receptor antagonists (acotiamide or Z-338).
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PMID:Prokinetics and fundic relaxants in upper functional GI disorders. 1894 Feb 66

Impaired gastric accommodation and gastric dysrhythmia are common in gastroparesis and functional dyspepsia. Recent studies have shown that synchronized gastric electrical stimulation (SGES) accelerates gastric emptying and enhances antral contractions in dogs. The aim of this study was to investigate the effects and mechanism of SGES on gastric accommodation and slow waves impaired by vagotomy in dogs. Gastric tone, compliance, and accommodation as well as slow waves with and without SGES were assessed in seven female regular dogs and seven dogs with bilateral truncal vagotomy, chronically implanted with gastric serosal electrodes and a gastric cannula. We found that 1) vagotomy impaired gastric accommodation that was normalized by SGES. The postprandial increase in gastric volume was 283.5 +/- 50.6 ml in the controlled dogs, 155.2 +/- 49.2 ml in the vagotomized dogs, and 304.0 +/- 57.8 ml in the vagotomized dogs with SGES. The ameliorating effect of SGES was no longer observed after application of N(omega)-nitro-L-arginine (L-NNA); 2) vagotomy did not alter gastric compliance whereas SGES improved gastric compliance in the vagotomized dogs, and the improvement was also blocked by L-NNA; and 3) vagotomy impaired antral slow wave rhythmicity in both fasting and fed states. SGES at the proximal stomach enhanced the postprandial rhythmicity and amplitude (dominant power) of the gastric slow waves in the antrum. In conclusion, SGES with appropriate parameters restores gastric accommodation and improves gastric slow waves impaired by vagotomy. The improvement in gastric accommodation with SGES is mediated via the nitrergic pathway. Combined with previously reported findings (enhanced antral contractions and accelerated gastric emptying) and findings in this study (improved gastric accommodation and slow waves), SGES may be a viable therapy for gastroparesis.
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PMID:Synchronized gastric electrical stimulation improves vagotomy-induced impairment in gastric accommodation via the nitrergic pathway in dogs. 1902 28


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