Effect of alosetron on responses to colonic distension in patients with irritable bowel syndrome

Delvaux, Michel; Louvel, Dominique; Mamet, Jean-Philippe; Campos-Oriola, R.; Frexinos, Jacques

doi:10.1046/j.1365-2036.1998.00375.x

Cited by 221 publications

(155 citation statements)

References 23 publications

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“…58,59 A clinical study of patients with IBS suffering from VH exhibited that alosetron, a 5-HT 3 receptor antagonist, can significantly improve gastrointestinal symptoms, including higher volume thresholds and reducing colonic compliance. 60 Subsequent to aversive rectal exciting, alosetron obviously reduces the emotional motor system of brain activity leading to modulation of the gut sensitivity. 61 In addition, tegaserod which is a partial agonist of 5-HT 4 receptor significantly reduced sensitivity to rectal distension and improved visceral sensation in both patients and healthy subjects.…”

Section: Serotoninmentioning

confidence: 99%

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

Farzaei

Bahramsoltani

Abdollahi

et al. 2016

J Neurogastroenterol Motil

146

122

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Irritable bowel syndrome (IBS) is the most common disorder referred to gastroenterologists and is characterized by altered bowel habits, abdominal pain, and bloating. Visceral hypersensitivity (VH) is a multifactorial process that may occur within the peripheral or central nervous systems and plays a principal role in the etiology of IBS symptoms. The pharmacological studies on selective drugs based on targeting specific ligands can provide novel therapies for modulation of persistent visceral hyperalgesia. The current paper reviews the cellular and molecular mechanisms underlying therapeutic targeting for providing future drugs to protect or treat visceroperception and pain sensitization in IBS patients. There are a wide range of mediators and receptors participating in visceral pain perception amongst which substances targeting afferent receptors are attractive sources of novel drugs. Novel therapeutic targets for the management of VH include compounds which alter gut-brain pathways and local neuroimmune pathways. Molecular mediators and receptors participating in pain perception and visceroperception include histamine-1 receptors, serotonin (5-hydrodytryptamine) receptors, transient receptor potential vanilloid type I, tachykinins ligands, opioid receptors, voltage-gated channels, tyrosine receptor kinase receptors, protease-activated receptors, adrenergic system ligands, cannabinoid receptors, sex hormones, and glutamate receptors which are discussed in the current review. Moreover, several plant-derived natural compounds with potential to alleviate VH in IBS have been highlighted. VH has an important role in the pathology and severity of complications in IBS. Therefore, managing VH can remarkably modulate the symptoms of IBS. More preclinical and clinical investigations are needed to provide efficacious and targeted medicines for the management of VH. (J Neurogastroenterol Motil 2016;22:558-574)

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Section: Serotoninmentioning

confidence: 99%

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

Farzaei

Bahramsoltani

Abdollahi

et al. 2016

J Neurogastroenterol Motil

146

122

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“…Antagonism of the 5-HT3 receptor results in slower small bowel and colonic transit times, a reduction in intestinal secretion, increased stool firmness, and an increase in colonic compliance [29,37] . There is also data suggesting that antagonism of this receptor in the amygdala, dorsal pons and ventral striatum may be responsible for perceived improvement in visceral pain, though the exact mechanism is unclear [38,39] .…”

Section: -Ht3 Antagonistsmentioning

confidence: 99%

Updates on treatment of irritable bowel syndrome

Hammerle¹,

Surawicz²

2008

WJG

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Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder characterized by abdominal pain and discomfort in association with altered bowel habits. It is estimated to affect 10%-15% of the Western population, and has a large impact on quality of life and (in)direct healthcare costs. IBS is a multifactorial disorder involving dysregulation within the brain-gut axis, and it is frequently associated with gastrointestinal motor and sensory dysfunction, enteric and central nervous system irregularities, neuroimmune dysregulation, and postinfectious inflammation. As with other functional medical disorders, the treatment for IBS can be challenging. Conventional therapy for those with moderate to severe symptoms is largely unsatisfactory, and the development of new and effective drugs is made difficult by the complex pathogenesis, variety of symptoms, and lack of objective clinical findings that are the hallmark of this disorder. Fortunately, research advances over the past several decades have provided insight into potential mechanisms responsible for the pathogenesis of IBS, and have led to the development of several promising pharmaceutical agents. In recent years there has been much publicity over several of these new IBS medications (alosetron and tegaserod) because of their reported association with ischemic colitis and cardiovascular disease. While these agents remain available for use under restricted prescribing programs, this highlights the need for continued development of safe and effective medication for IBS. This article provides a physiologicallybased overview of recently developed and frequently employed pharmaceutical agents used to treat IBS, and discusses some non-pharmaceutical options that may be beneficial in this disorder.

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“…Alosetron has been demonstrated, on isobaric phasic distension studies, to increases the compliance of the colon to distension. This was postulated to contribute to changes in perception of colonic distension (Delvaux et al 1998). Alosetron increases the number and propagation length of high amplitude colonic contractions which results in a paradoxical decrease in stool frequency (Clemens et al 2002).…”

Section: Alosetronmentioning

confidence: 99%

Serotonin receptor modulators in the treatment of irritable bowel syndrome

Fayyaz

Lackner

2008

TCRM

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Abstract:The aim of this article is to review the pathophysiology and clinical role of serotonin receptor modulators used in the treatment of irritable bowel syndrome. Serotonin is an important monoamine neurotransmitter that plays a key role in the initiation of peristaltic and secretory refl exes, and in modulation of visceral sensations. Several serotonin receptor subtypes have been characterized, of which 5HT3, 5HT4, and 5HT1b are the most important for GI function. 5HT4 agonists (eg, tegaserod) potentiate peristalsis initiated by 5HT1 receptor stimulation. 5HT4 agonists are therefore useful in constipation predominant form of IBS and in chronic constipation. 5HT3 antagonists (Alosetron and Cilansetron) prevent the activation of 5HT3 receptors on extrinsic afferent neurons and can decrease the visceral pain associated with IBS. These agents also retard small intestinal and colonic transit, and are therefore useful in diarrhea-predominant IBS. Tegaserod has been demonstrated in several randomized, placebo controlled trials to relieve global IBS symptoms as well as individual symptoms of abdominal discomfort, number of bowel movements and stool consistency. Several randomized, controlled trials have shown that alosetron relieves pain, improves bowel function, and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome. However, ischemic colitis and severe complications of constipation have been major concerns leading to voluntary withdrawal of Alosetron from the market followed by remarketing with a comprehensive risk management program.

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Effect of alosetron on responses to colonic distension in patients with irritable bowel syndrome

Cited by 221 publications

References 23 publications

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

Updates on treatment of irritable bowel syndrome

Serotonin receptor modulators in the treatment of irritable bowel syndrome

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