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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Manabe, Noriaki Wong, Banny S. Camilleri, Michael |
| Description | Country affiliation: United States Author Affiliation: Manabe N ( Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN 55905, USA.) |
| Abstract | IMPORTANCE OF THE FIELD: Gastrointestinal (GI) dysmotility is an important mechanism in functional GI disorders (FGIDs) including constipation, irritable bowel syndrome, functional dyspepsia, and gastroparesis. 5-hydroxytryptamine(4) (5-HT(4)) receptors are targets for the treatment of GI motility disorders. However, older 5-HT(4) receptor agonists had limited clinical success because they were associated with changes in the function of the cardiac HERG potassium channel. AREAS COVERED IN THIS REVIEW: We conducted a PubMed search using the following key words alone or in combination: 5-HT(4), safety, toxicity, pharmacokinetics, pharmacodynamics, clinical trial, cardiac, hERG, arrhythmia, potassium current, elderly, prucalopride, ATI-7505, and velusetrag (TD-5108), to review mechanisms of action, clinical efficacy, safety and tolerability of three new-generation 5-HT(4) receptor agonists. WHAT THE READER WILL GAIN: Prucalopride, ATI-7505, and velusetrag (TD-5108) are highly selective, high-affinity 5-HT(4) receptor agonists that are devoid of action on other receptors within their therapeutic range. Their efficacy has been demonstrated in pharmacodynamic studies which demonstrate acceleration of colonic transit and, to a variable degree, in clinical trials that significantly relieve chronic constipation. Currently available evidence shows that the new 5-HT(4) receptor agonists have safe cardiac profiles. TAKE HOME MESSAGE: New-generation 5-HT(4) receptor agonists and future drugs targeting organ-specific splice variants are promising approaches to treat GI dysmotility, particularly colonic diseases. |
| File Format | HTM / HTML |
| ISSN | 13543784 |
| Issue Number | 6 |
| Volume Number | 19 |
| e-ISSN | 17447658 |
| Journal | Expert Opinion on Investigational Drugs |
| Language | English |
| Publisher | Taylor & Francis |
| Publisher Date | 2010-06-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Analytical Chemistry Discipline Pharmacology Gastrointestinal Motility Drug Effects Serotonin 5-ht4 Receptor Agonists Serotonin Receptor Agonists Therapeutic Use Animals Clinical Trials As Topic Colonic Diseases, Functional Drug Therapy Physiopathology Drug Delivery Systems Gastrointestinal Agents Adverse Effects Pharmacology Gastrointestinal Diseases Humans Journal Article Review |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Pharmacology (medical) |
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