- StatPearls: Alosetron [BOOK]StatPearls. StatPearls Publishing: Treasure Island (FL)BOOK
- Alosetron is a medication used to manage and treat severe diarrhea-predominant irritable bowel syndrome (IBS-D). It is in the class of 5-HT receptor antagonist medications. This activity outlines the indications, action, and contraindications for alosetron as a valuable agent in IBS-D management. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e…
- Regional brain activation during rectal distention and attenuation with alosetron in a nonhuman primate model of irritable bowel syndrome. [Journal Article]
- Greater understanding of the mechanism that mediates visceral pain and hypersensitivity associated with irritable bowel syndrome (IBS) would facilitate the development of effective therapeutics to manage these symptoms. An objective marker associated with the underlying mechanisms of visceral pain and hypersensitivity could be used to guide therapeutic development. The current study examined brai…
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- A Narrative Review of Irritable Bowel Syndrome with Diarrhea: A Primer for Primary Care Providers. [Review]
- Irritable bowel syndrome with diarrhea (IBS-D) is a chronic disorder of gut-brain interaction, characterized by recurrent abdominal pain in association with more frequent, loose stools. The pathophysiology of irritable bowel syndrome (IBS) includes disordered gut motility, alterations in gut microbiota, neural-hormonal system abnormalities, immune reactivity, and visceral hypersensitivity. Timely…
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- AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Diarrhea. [Practice Guideline]
- CONCLUSIONS: The panel agreed on 8 recommendations for the management of patients with IBS-D. The panel made conditional recommendations for eluxadoline, rifaximin, alosetron, (moderate certainty), loperamide (very low certainty), tricyclic antidepressants, and anstispasmodics (low certainty). The panel made a conditional recommendation against the use of selective serotonin reuptake inhibitors (low certainty).
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- Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility. [Review]
- Irritable bowel syndrome with diarrhoea (IBS-D) and functional diarrhoea (FDr) are the two major functional bowel disorders characterized by diarrhoea. In spite of their high prevalence, IBS-D and FDr are associated with major uncertainties, especially regarding their optimal diagnostic work-up and management. A Delphi consensus was performed with experts from 10 European countries who conducted …
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- Expression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine. [Journal Article]
- The gastrointestinal hormone, insulin-like peptide 5 (INSL5), is found in large intestinal enteroendocrine cells (EEC). One of its functions is to stimulate nerve circuits that increase propulsive activity of the colon through its receptor, the relaxin family peptide 4 receptor (RXFP4). To investigate the mechanisms that link INSL5 to stimulation of propulsion, we have determined the localisation…
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- In silico Repurposing of Drugs for pan-HDAC and pan-SIRT Inhibitors: Consensus Structure-based Virtual Screening and Pharmacophore Modeling Investigations. [Journal Article]
- CONCLUSIONS: The consensus approach enabled selection of the best performing drug molecules according to different software, and good scores against isoforms (virtual pan-HDAC and pan-SIRT inhibitors). The study not only proposes potential drugs to be repurposed for HDAC and SIRT-related diseases but also provides insights for designing potent de novo derivatives.
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- Review Article: Current and future treatment approaches for IBS with diarrhoea (IBS-D) and IBS mixed pattern (IBS-M). [Review]
- CONCLUSIONS: The treatment of IBS-D/M ideally involves a multidisciplinary approach of primary care, gastroenterologist and psychologist. Treatment often involves both non-pharmacological and pharmacological therapies. Future therapies may include faecal microbial transplant, Crofelemer and serotonin antagonists, but further studies are needed.
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- New approaches to ondansetron and alosetron inspire a versatile, flow photochemical method for indole synthesis. [Journal Article]
- An oxidative photocyclisation of N-arylenaminones to indoles is described, that mirrors the Fischer indole synthesis but uses anilines in place of arylhydrazines. Its value is exemplified with new approaches to the WHO-listed APIs ondansetron and alosetron.
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- Diarrhea-Predominant and Constipation-Predominant Irritable Bowel Syndrome: Current Prescription Drug Treatment Options. [Review]
- Irritable bowel syndrome (IBS) is a heterogenous disease with a variety of therapeutic options, including eight prescription drugs approved for use in IBS in the USA. Choosing among the myriad treatment options requires attention to patient preferences both on clinical outcomes and costs associated with treatment. We performed a narrative review of the literature to summarize these important dete…
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- In silico screening of neurokinin receptor antagonists as a therapeutic strategy for neuroinflammation in Alzheimer's disease. [Journal Article]
- Neuroinflammation is one of the detrimental factors leading to neurodegeneration in Alzheimer's disease (AD) and other neurodegenerative disorders. The activation of microglial neurokinin 1 receptor (NK1R) by substance P (SP) enhances neuroinflammation which is mediated through pro-inflammatory pathways involving NFkB, ERK1/2, and P38 and thus projects the scope and importance of NK1R inhibitors.…
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- Comparative effectiveness of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: a network meta-analysis of randomized controlled studies. [Journal Article]
- CONCLUSIONS: This NWM showed that 5-HT3 receptor antagonists performed better in comparison to control drugs. Consequently, this class of drugs may play an important role in improving the debilitating symptoms in NC-IBS patients, in particular those with diarrhea.
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- Contrasting Clinician and Insurer Perspectives to Managing Irritable Bowel Syndrome: Multilevel Modeling Analysis. [Journal Article]
- Insurance coverage is an important determinant of treatment choice in irritable bowel syndrome (IBS), often taking precedence over desired mechanisms of action or patient goals/values. We aimed to determine whether routine and algorithmic coverage restrictions are cost-effective from a commercial insurer perspective.
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- Sex-Gender Differences in the Effectiveness of Treatment of Irritable Bowel Syndrome: A Systematic Review. [Review]
- CONCLUSIONS: Sex-gender can be a determining factor in the effectiveness of IBS treatment. Due to the limited number of studies per treatment option, no recommendations can be made on the choice of a specific treatment. It is clear, however, that so as not to miss beneficial treatment options for either sex, the inclusion, analysis and description of data on the basis of sex is of the utmost importance.
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- Estrogen and serotonin enhance stress-induced visceral hypersensitivity in female rats by up-regulating brain-derived neurotrophic factor in spinal cord. [Journal Article]
- CONCLUSIONS: Serotonin-mediated activation of 5HT3A receptors in the spinal cord drives the development of enhanced female-specific VHS in our two hit CPS+CAS through up-regulation of spinal cord ERα.
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- Management of irritable bowel syndrome with diarrhea: focus on eluxadoline. [Journal Article]
- CONCLUSIONS: IBS-D can be effectively managed in the primary care setting in the absence of alarm features. Benefits and risks of pharmacologic interventions should be weighed during treatment selection.
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- High-resolution structures of multiple 5-HT3AR-setron complexes reveal a novel mechanism of competitive inhibition. [Journal Article]
- Serotonin receptors (5-HT3AR) play a crucial role in regulating gut movement, and are the principal target of setrons, a class of high-affinity competitive antagonists, used in the management of nausea and vomiting associated with radiation and chemotherapies. Structural insights into setron-binding poses and their inhibitory mechanisms are just beginning to emerge. Here, we present high-resoluti…
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- Comparing Costs and Outcomes of Treatments for Irritable Bowel Syndrome With Diarrhea: Cost-Benefit Analysis. [Journal Article]
- CONCLUSIONS: Costs are critical determinants of IBS treatment value to patients and insurers, but different costs drive patient and insurer treatment preferences. Divergent cost drivers appear to explain misalignment between patient and insurer IBS treatment preferences in practice.
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- Pharmacologic Treatments for Irritable Bowel Syndrome: an Umbrella Systematic Review. [Systematic Review]
- CONCLUSIONS: Evidence for 5-HT3 antagonists, 5-HT4 agonists and GCC agonists, antispasmodics, and alosetron were suggestive for the treatment of IBS. However, owing to the risk of bias in randomization methods, the results for GCC should be interpreted with caution.
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- Best management of irritable bowel syndrome. [Review]
- Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction which can have a considerable impact on quality of life. Following diagnosis, timely and evidence-based management is vital to the care of patients with IBS, aiming to improve outcomes, and enhance patient satisfaction. Good communication is paramount, and clinicians should provide a clear explanation about the disorder,…
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- An update on efficacy and safety considerations for the latest drugs used to treat irritable bowel syndrome. [Review]
- CONCLUSIONS: Anti-spasmodics are used as the first-line treatment in pain-predominant IBS and IBS-D, among which calcium channel blockers and neurokinin-type 2 receptor antagonists seem to replace anti-cholinergic drugs. As second-line treatments, rifaximin is considered to be the best for IBS-D though it has lower efficacy than alosetron and eluxadoline. For IBS-C, linaclotide is the most effective and the safest second-line therapy, following laxatives/fibers, which may be replaced by tenapanor, in the future. When moderate to severe IBS is associated with severe pain or comorbid psychological disorders, gut-brain neuromodulators could also be prescribed. Regarding all this, there is still a paramount need to conduct careful clinical studies on efficacy, safety and cost-effectiveness of current approved and non-approved treatments.
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- Table: Safety of drugs for IBS in pregnancy and lactation (online only). [Journal Article]Med Lett Drugs Ther. 2020 03 23; 62(1594):e48-e49.ML
- Drugs for Irritable Bowel Syndrome. [Journal Article]Med Lett Drugs Ther. 2020 Mar 23; 62(1594):25-32.ML
- CSTI-300 (SMP-100); a Novel 5-HT3 Receptor Partial Agonist with Potential to Treat Patients with Irritable Bowel Syndrome or Carcinoid Syndrome. [Journal Article]
- The 5-hydroxytryptamine (5-HT) (serotonin) 5-HT3 receptor represents a clinical target for antagonists to deliver symptomatic relief to patients with diarrhea-predominant irritable bowel syndrome (IBS-d) or carcinoid syndrome. Unfortunately, this pharmacological strategy can present side effects (e.g., severe constipation). The present study investigates the potential of a novel 5-HT3 receptor pa…
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- Pharmacological evaluation of a novel corticotropin-releasing factor 1 receptor antagonist T-3047928 in stress-induced animal models in a comparison with alosetron. [Journal Article]
- CONCLUSIONS: T-3047928 is an orally active CRF1 antagonist that demonstrated potent inhibitory effects in stress-associated IBS models with no effect on normal defecation. Therefore, it is suggested that T-3047928 may have a potency as a novel option for IBS-D therapy with minimal constipation risk.
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- Sex-Related Differences in Pharmacokinetics and Pharmacodynamics of Frequently Prescribed Drugs: A Review of the Literature. [Review]
- While there is considerable evidence about sex-related differences between men and women in drug metabolism, efficacy and safety of frequently prescribed drugs such as analgesics, tranquillizers, statins and beta-blockers, clinicians' awareness of the implications on dosing and adverse event monitoring in routine practice is inadequate. Some drugs are more effective in men than women (e.g. ibupro…
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- Current and emerging pharmacological approaches for treating diarrhea-predominant irritable bowel syndrome. [Review]
- Introduction: Irritable bowel syndrome with diarrhea (IBS-D) is among the most common functional gastrointestinal (GI) disorders and is associated with impaired quality of life, increased health-care utilization, and significant costs to patients and society. The treatment of IBS is typically hierarchal with initial therapies consisting of dietary and lifestyle modifications. Pharmacotherapy with…
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- Current US Food and Drug Administration-Approved Pharmacologic Therapies for the Treatment of Irritable Bowel Syndrome with Diarrhea. [Review]
- Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain and alterations in stool form and/or frequency, leading to reduced quality of life. Pharmacologic agents currently approved by the US Food and Drug Administration for treatment of IBS with diarrhea (IBS-D) in adults are the nonsystemic antibiotic rifaximin, the mixed µ- and κ-opioid receptor agonist/δ-op…
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- Management of irritable bowel syndrome with diarrhea: a review of nonpharmacological and pharmacological interventions. [Review]
- Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) condition involving numerous potential causative factors (e.g. alterations in gut microbiota, motility, brain-gut axis). Several interventions are available for the management of patients with IBS, but no universal management algorithm currently exists. The aim of this article is to review interventions that may be considered in the…
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- Anti-inflammatory effects of alosetron mediated through 5-HT3 receptors on experimental colitis. [Journal Article]
- Development of new medicine with fewer deleterious effects and more efficacies for treatment of inflammatory bowel disease is needed. 5-Hydroxytryptamine 3 receptor (5-HT3R) antagonists have exhibited analgesic and anti-inflammatory features in vitro and in vivo. The present study was designed to evaluate the anti-inflammatory effect of alosetron, a 5-HT3R antagonist, on trinitrobenzenesulfonic a…
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