Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irritable bowel syndrome (IBS) is the most common chronic gastrointestinal (GI) disorder, affecting about 20% of the world's population. Chronic abdominal pain or discomfort relieved by defecation and associated with altered bowel habits are the mainstay in diagnosis. The pathophysiology of IBS remains unknown. This biopsychosocial disorder involves dysregulation of the nervous system, altered intestinal motility, and increased visceral sensitivity. All of these result from dysregulation of the bidirectional communication between the gut with its enteric nervous system and the brain (the brain-gut axis), modulated by various psychosocial and environmental factors (e.g. infection, inflammation). Numerous neurotransmitters are found in the brain and gut that regulate GI activities, including 5-hydroxytryptamine (5-HT, serotonin) and its 5-HT3 and 5-HT4 receptors. The current approach to IBS patients is based on a positive diagnosis of the symptom complex, exclusion of underlying organic disease, and institution of a therapeutic trial. Traditional symptomatic treatment has included antidiarrheals, laxatives and bulking agents/fiber, low-dose tricyclic antidepressants, antispasmodics for pain, and "alternative" therapies (e.g. psychotherapy, hypnotherapy). The scientific evidence supporting this therapy is limited. Novel approaches include visceral analgesics and serotonin agonists and antagonists. In patients with severe diarrhea, 5-HT3 receptor antagonists (e.g. alosetron) and selective M3-type anticholinergics are indicated, in constipation 5-HT4 agonists (e.g. tegaserod), and in pain alfa2-adrenergics (e.g. clonidine), cholecystokinin antagonists, kappa-opioid agonists (e.g. fedotozine), and neurokinin antagonists; some of these agents are still being investigated. Understanding the brain-gut axis is crucial in the development of effective therapies for IBS.
Med Sci Monit 2004 Jun
PMID:The brain-gut axis in irritable bowel syndrome--clinical aspects. 1517 82

Postoperative nausea and vomiting (PONV) affects approximately one third of patients and may lead to aspiration, dehiscence, esophageal rupture, and increased treatment costs if inadequately controlled. An important therapeutic option for prevention of PONV is 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists. Nonetheless, therapeutic failure sometimes occurs. Metabolism by the cytochrome P450 (CYP) system differs among the 5-HT3 receptor antagonists, and provides a rational explanation for decreased therapeutic efficacy in some patients. Four of the 5-HT3 receptor antagonist agents (dolasetron, ondansetron, palonosetron, and tropisetron) are metabolized in various degrees via CYP2D6, an isoform subject to marked genetic polymorphism. In patients with duplicate CYP2D6 alleles, degradation into inactive metabolites occurs rapidly with these four 5-HT3 receptor antagonists, resulting in decreased efficacy for preventing PONV. Granisetron is the only agent in this class that is not metabolized via CYP2D6. Instead, granisetron is metabolized via the CYP3A4 isoform, which is not subject to significant genetic polymorphism. CYP2D6 genotype screening prior to PONV treatment may allow for modification of antiemetic dosing. An alternative is to use a 5-HT3 agent that is metabolized independently of the CYP2D6 isoform, such as granisetron, that would obviate the need for genotyping and may lead to improved prophylaxis of PONV.
Med Sci Monit 2005 Oct
PMID:Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. 1619 15