Irritable Bowel Syndrome

G A Hicks, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA © 2007 Elsevier Ltd. All Rights Reserved.

6.29.1 Disease State 644

6.29.1.1 Epidemiology and Socioeconomic Burden 644

6.29.1.2 Physical Description of Symptoms 644

6.29.2 Disease Basis 645

6.29.2.1 Basic Neurophysiology of the Gastrointestinal Tract 645

6.29.2.1.1 Neuronal control of gastrointestinal function 645

6.29.2.1.2 Key roles of 5-hydroxytryptamine in gastrointestinal function 646

6.29.2.2 Clinical Observations with Potential Links to Irritable Bowel Syndrome

Symptoms 648

6.29.2.2.1 Gastrointestinal dysmotility 648

6.29.2.2.2 Altered brain-gut axis communication 649

6.29.2.2.3 Visceral sensitivity and hypersensitivity 649

6.29.2.2.4 5-Hydroxytryptamine signaling abnormalities: role of altered release and/or reuptake 649

6.29.2.2.5 Role of stress/psychosocial factors 650

6.29.2.2.6 Previous infection 650

6.29.2.2.7 Immune-system alterations/gut flora/food allergy 651

6.29.2.2.8 Genetic links 651

6.29.3 Experimental Disease Models 651

6.29.4 Clinical Trial Issues 653

6.29.5 Current Treatment of Irritable Bowel Syndrome 653

6.29.5.1 Drugs Targeting the Multiple-Symptom Complex of Irritable

Bowel Syndrome 654

6.29.5.1.1 Serotonergic agonists and antagonists 654

6.29.5.2 Drugs Targeting Single Symptoms 658

6.29.5.2.1 Dietary aids and bulking agents 658

6.29.5.2.2 Laxatives 658

6.29.5.2.3 Stool softeners 658

6.29.5.2.4 Antidiarrheal agents 658

6.29.5.2.5 Antispasmodic agents 659

6.29.5.2.6 Antidepressants 659

6.29.6 Unmet Medical Needs 660

6.29.7 New Research Areas 660

6.29.7.1 Cilansetron (5HT3 Antagonist) 662

6.29.7.2 Renzapride 662

6.29.7.3 Neurokinin Receptor Modulators 662

6.29.7.4 Opioid Receptor Antagonists 663

6.29.7.5 CRF-1 Antagonists 664

6.29.7.6 Clonidine 664

6.29.7.7 Cholecystokinin Receptor Antagonists 664

6.29.7.8 Chloride Channel Openers 665

6.29.7.9 Cannabinoid Receptor Modulators 665 References 665

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