Drug development for functional @entity344 is complex. These conditions involve central and peripheral physiological changes, together with psychological factors. Methodological problems have included a poor appreciation of the physiological and psychological correlates of @entity1 ' symptoms, a lack of animal models of proven relevance, and safety issues. Government, @entity1 pressure groups and the Internet can also influence a drug's success. Most recent interest has focused on the @entity750 ( @entity750 ) modifying drugs. @entity4392 has been withdrawn in some countries because of concerns related to @entity1162 and @entity943 . The 5-HT3 antagonists, developed to modify visceral sensation, have caused @entity1142 ; alosetron, also withdrawn, caused @entity1960 . The 5-HT4 agonists induce peristalsis; tegaserod and @entity17627 , both delayed in their development due to issues of safety and efficacy, benefit @entity1 with ' @entity1744 or idiopathic @entity1142 . 5-HT1 agonists improve impaired gastric accommodation and symptoms in @entity1 with functional @entity2210 . Antidepressants also affect @entity750 metabolism. Previous examples of success in this area involved drugs targeted at peripheral receptors mediating motor function or secretion. Modification of sensory function is a much more challenging objective. The experience with @entity750 modifying drugs has been mixed, and some important lessons are there to be learnt.

Review article: the complexity of drug development for XXXX .

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity4392 :: ('MESH:D020117', 'Chemical') :: ['Cisapride'] @entity344 :: ('MESH:D005767', 'Disease') :: ['gastrointestinal disorders'] @entity17627 :: ('MESH:C406662', 'Chemical') :: ['prucalopride'] @entity1960 :: ('MESH:D003092', 'Disease') :: ['ischaemic colitis'] @entity750 :: ('MESH:D012701', 'Chemical') :: ['serotonin', '5-HT'] @entity2210 :: ('MESH:D004415', 'Disease') :: ['dyspepsia'] @entity1162 :: ('MESH:D008133', 'Disease') :: ['QT prolongation'] @entity1142 :: ('MESH:D003248', 'Disease') :: ['constipation'] @entity943 :: ('MESH:D001145', 'Disease') :: ['cardiac arrhythmias'] @entity1744 :: ('MESH:D043183', 'Disease') :: ["constipation-predominant' irritable bowel syndrome"]
@entity1744 :: (MESH:D043183,Disease) :: ['irritable bowel syndrome']
