Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cisapride and metoclopramide are used clinically in the treatment of gastro-oesophageal reflux disease and also in a variety of motility disorders of the gastrointestinal tract. Their prokinetic effect is thought to be due to the augmentation of acetylcholine release from the myenteric plexus, an effect likely to be mediated through the stimulation of 5-HT4 receptors. The role of 5-HT4 receptors in the control of intestinal motility in man and animals is not clear, therefore we have investigated their role in the control of small intestinal transit in the rat. Radioactive microspheres were administered into the proximal duodenum of fasted conscious rats through an indwelling cannula. The extent of small intestinal transit was examined by determining the distribution of the microspheres within the intestine. Following i.p. injection small intestinal transit was inhibited (78%) by atropine (3 mg/kg), suggesting the presence of a basal cholinergic influence. Furthermore, in the presence of p-amino clonidine intestinal transit was stimulated (126%) by bethanechol (3 mg/kg). The 5-HT4 receptor agonists cisapride (1.0 mg/kg) and zacopride (1.0 mg/kg) failed to increase small intestinal transit. The 5-HT4 receptor selective antagonist GR125487 (1 mg/kg) was also without effect. These data suggest that 5-HT4 receptors are not involved in the control of small intestinal transit in the fasted conscious rat.
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PMID:5-HT4 receptors are not involved in the control of small intestinal transit in the fasted conscious rat. 869 80

Noncardiac chest pain (NCCP) is a common condition with significant morbidity and economic implications. Psychological factors, gastroesophageal reflux disease (GERD), alteration in pain perception, and esophageal dysmotility play an important role in the pathogenesis of the disorder. Proton pump inhibitor (PPI) therapy is the most effective medical intervention for the treatment of GERD-related NCCP, as well as the most cost-effective diagnostic strategy for this condition. Pain modulators such as tricyclic antidepressants, trazodone, and selective serotonin reuptake inhibitors infer a visceral analgesic effect and consequently are the treatment of choice for patients with non-GERD-related NCCP. Furthermore, cognitive behavioral therapy has also been shown to be useful in the management of subset of patients with non-GERD-related NCCP. Newer therapeutic modalities and interventions such as lower esophageal sphincter injection of botulinum toxin in NCCP patients with spastic esophageal motility disorders, theophylline, and 5-HT4 receptor agonists may supplement or replace current treatment for non-GERD-related NCCP. Future compounds may include new visceral analgesics or medications that interfere with the development of peripheral or central sensitization.
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PMID:Noncardiac Chest Pain. 1523 2

Serotonin 5-hydroxytryptamine 4(5-HT4) receptor agonists have been widely prescribed as a prokinetics drug for patients with gastro-esophageal reflux disease and functional dyspepsia. QX100626, one of the 5-HT4 receptor agonists, has been studied as a promising agent for this clinical use. The objective of the present study was to identify possible target organs of toxicity and propose a non-toxic dose of QX100626 for clinical usage. After single lethal dose oral and intravenous testing in rodents, some signs indicative of adverse CNS effects were observed. The minimum toxic dose of QX100626 for a single oral administration for dogs was 90.0mg/kgb.w., and the severe toxic dose was more than 300mg/kgb.w. The No Observed Adverse Effect Level (NOAEL) of QX100626 by daily oral administration for rats and dogs was 20mg/kg and 10mg/kg, respectively, whereas the minimum toxic dosages were 67 and 30mg/kg, respectively. All of the adverse effects suggested that kidney, digestive tract, as well as nervous, hematological, and respiratory systems might be the target organs of toxicity for humans induced by QX100626. The compound could be a safe alternative to other existing prokinetic agents for the treatment of functional bowel disorders.
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PMID:Acute and subchronic toxicities of QX100626, a 5-HT4 receptor agonist, in rodents and Beagle dogs. 2510 57