Zelnorm (tegaserod) / Novartis - LARVOL DELTA

Single-Center Experience with Concomitant Use of Novel and Off-Label Prescriptions for Chronic Constipation (ACG 2024) - "Charts were reviewed for prescriptions of at least 1 of 8 pharmacotherapies: linaclotide, lubiprostone , plecanatide , prucalopride, tenapanor , tegaserod, pyridostigmine, and colchicine. 405 patients were evaluated for chronic constipation, of which 138 (34%) received one or more prescription-based therapies. The most common diagnoses supporting these prescriptions are listed in Table 1. 110 patients (79.7%) were prescribed monotherapy, 23 (16.67%) given dual therapy simultaneously, 4 (2.8%) given three agents simultaneously, and only 1 (0.7%) given four agents simultaneously."

Clinical • Constipation • Gastroenterology • Gastrointestinal Disorder

Tegaserod Stimulates 5-HT4 Serotonin Receptors in the Isolated Human Atrium. (PubMed, Int J Mol Sci) - "Tegaserod shifted the concentration-response curve of the force of contraction to serotonin to the right in HAPs, indicating that it is a partial agonist at 5-HT4 serotonin receptors in this model. We propose that the mechanism of action of tegaserod in HAPs involves cAMP-dependent phosphorylation of cardiac regulatory proteins."

Journal • Gastrointestinal Disorder • Inflammatory Bowel Disease

Integrated transcriptomics- and structure-based drug repositioning identifies drugs with proteasome inhibitor properties. (PubMed, Sci Rep) - "Here, we used an integrated drug repositioning approach based on transcriptomics data and structure-based virtual screening to identify compounds with gene signatures similar to three known proteasome inhibitors (PIs; bortezomib, MG-132, and MLN-2238)...Using this approach, we identified six compounds with PI properties ((-)-kinetin-riboside, manumycin-A, puromycin dihydrochloride, resistomycin, tegaserod maleate, and thapsigargin)...As shown with bortezomib, only manumycin-A, puromycin dihydrochloride, and tegaserod maleate resulted in excessive accumulation of ubiquitinated proteins and elevated HMOX1 expression. Taken together, our integrated drug repositioning approach and subsequent in vitro validation studies identified six compounds demonstrating properties similar to proteasome inhibitors."

Journal • Breast Cancer • Melanoma • Oncology • Solid Tumor • Targeted Protein Degradation • HMOX1

Gut Dysbiosis and Alterations of Gastrointestinal Motility as Drivers of Opioid-Induced Hyperalgesia (IASP 2024) - " Male and female C57Bl6J mice were treated with escalating doses of morphine (10-40 mg/kg, i.p.) for 4 days...To assess the role of gut motility, drug-naïve mice were treated with tegaserod, a peripherally-restricted serotonin agonist that increases gut motility, to determine if increasing gut motility was sufficient to replicate opioid-induced dysbiosis and withdrawal symptoms... Opioid withdrawal produces profound and protracted changes in gut microbiota, motility, and permeability in mice, which correlated with the development and duration of withdrawal-induced inflammation and hyperalgesia. Chronic opioid treatment and withdrawal in germ-free mice, lacking a gut microbiome, does not produce spinal inflammation nor does it result in persistent hyperalgesia. Imitating the increase in gut motility during withdrawal via pharmacological means is sufficient to elicit pain and neuroinflammation, while limiting opioid actions to the central nervous system prevents these..."

Dysbiosis • CNS Disorders • Gastrointestinal Disorder • Immunology • Inflammation • Pain

Current and future pharmacotherapies for the management of constipation-predominant irritable bowel syndrome. (PubMed, Expert Opin Pharmacother) - "Therefore, new therapies are being developed to speed up bowel movement and reduce constipation, with drugs such as linaclotide, plecanatide, lubiprostone, or tegaserod available to reduce IBS-C symptoms. Current clinical trials of new therapeutic options are not too successful and it seems that one of the plausible treatment options could be the multi-drug cocktail with some, or perhaps even all its ingredients emerging from drug re-purposing. Another important path that needs to be explored further in IBS-C patients is the adjustment of dietary habits and/or introduction of dietary or nutritional intervention."

Journal • Review • Constipation • Gastroenterology • Gastrointestinal Disorder

RISK OF CONSTIPATION WITH ANTI-OBESITY MEDICATION AND CURRENT PRESCRIBING PATTERN LANDSCAPE IN MANAGING THE SIDE EFFECT (DDW 2024) - "We then determined whether these patients were prescribed a medication for constipation (plecanatide linaclotide tegaserod lubiprostone polyethylene glycol (PEG) magnesium oxide lactulose bisacodyl senna sodium picosulfate tenapanor prucalopride)...8% (7/145) diethylpropion...Liraglutide and phentermine-topiramate had the highest constipation rates. Black patients had higher rate of new constipation diagnosis and treatment compared to White patients. Semaglutide had the least risk for requiring constipation medication."

Adverse events • Constipation • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Obesity

IMPLICATIONS OF POPULAR TRENDING ANTI-OBESITY MEDICATIONS - AN INCREASE IN HEALTHCARE COST AND UTILIZATION FOR THE POPULATION WITH CONSTIPATION (DDW 2024) - "Inclusion criteria included obese patients started on an AOM (per the 0 AGA Guideline on the Pharmacological Interventions for Adults with Obesity - semaglutide liraglutide phentermine-topiramate phentermine naltrexone-bupropion diethylpropion) who subsequently developed constipation after one week to twelve months after starting the AOM...The search was then narrowed to patients who were prescribed a constipation medication: plecanatide linaclotide tegaserod lubiprostone polyethylene glycol (PEG) magnesium oxide lactulose bisacodyl senna sodium picosulfate tenapanor prucalopride...Patients on AOM who develop constipation appear to have a threefold increase in ED visits and inpatient admissions. The average annual cost of constipation medication alone is $5 485. 04 per person."

Clinical • HEOR • Constipation • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Obesity

CLINICAL EFFICACY AND ELECTROGASTROGRAPHIC CHANGES OF TEGASEROD VS. DOMPERIDONE IN PATIENTS WITH FUNCTIONAL DYSPEPSIA WITH GASTRIC DYSRHYTHMIA (DDW 2024) - "Tegaserod showed a significant improvement both symptomatically and electrogastrographically compared to domperidone in patients with FD presenting with dysrhythmia on EGG. Further studies with a larger number of patients and longer treatment duration are needed to determine its clinical use."

Clinical • Cardiovascular • Celiac Disease • CNS Disorders • Dyspepsia • Immunology

Prevalence and Choice of Pharmacologic Management of Functional Dyspepsia and Irritable Bowel Syndrome During Pregnancy (ACG 2023) - "Pylori Antibiotics = Metronidazole, Clarithromycin, Levofloxacin, Tetracycline, Doxycycline, Tinidazole, Nitazoxanide, Rifabutin. Anti-Diarrheals = Loperamide, Diphenoxylate, Bismuth Salicylate. Bile Acid Sequestrants = Cholestyramine, Colesevelam, Colestipol. Bowel Stimulants = Bisacodyl, Sennosides. Exposure to IBS or FD medications was significantly elevated in IBSFD compared to NONE. 17,984 of 48,208 IBSFD patients (37%) were exposed to proton pump inhibitors compared to 266,835 of 3,046,065 (9%) of NONE (OR 6.20; 95% CI 6.08 - 6.52). 1.4% of IBSFD were exposed to Rifaximin compared to 0.032% of NONE (OR 44.44; CI 40.19 - 49.14)."

Dyspepsia • Gastrointestinal Disorder

Small Organic Compounds Mimicking the Effector Domain of Myristoylated Alanine-Rich C-Kinase Substrate Stimulate Female-Specific Neurite Outgrowth. (PubMed, Int J Mol Sci) - "We found that epigallocatechin, amiodarone, sertraline, tegaserod, and nonyloxytryptamine bind to a monoclonal antibody against the ED peptide, and compounds stimulate neurite outgrowth in cultured cerebellar granule cells of female mice only. Therefore, a search for compounds that act in males appears warranted."

Journal • CNS Disorders • Orthopedics • MARCKS

The RNA m6A reader YTHDF1 is required for acute myeloid leukemia progression. (PubMed, Cancer Res) - "Moreover, tegaserod reduced the viability of patient-derived AML cells in vitro and prolonged survival in patient-derived xenograft models. Together, our study defines YTHDF1 as an integral regulator of AML progression by regulating the expression of m6A-modified mRNAs, which might serve as a potential therapeutic target for AML."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • YTHDF1

Lactobacillus rhamnosus GG supernatant promotes intestinal mucin production through regulating 5-HT4R and gut microbiota. (PubMed, Food Funct) - "Six-week-old C57BL/6J mice were randomized into 3 groups, and were treated with De-Man Rogosa and Sharpe broth (MRS group), tegaserod maleate (tegaserod group) and LGG supernatant (LGGs group) by gavage, respectively...Our results suggested that LGGs could upregulate 5-HT4R to promote MUC2 production, as well as modulate the gut microbiota, thus improving the defecation function in mice. This finding might provide evidence for the application of diet supplementary LGG in relieving gastrointestinal motility disorders."

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • Transplantation • MUC2

Tegaserod maleate exhibits antileukemic activity by targeting TRPM8. (PubMed, Biomed Pharmacother) - "Importantly, TRPM8 is overexpressed in AML patients, indicating that it is a new prognostic factor in AML. Collectively, our work demonstrates the anti-AML effects of tegaserod maleate via targeting TRPM8 and indicates that TRPM8 is a regulator of leukemogenesis with therapeutic potential in AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FOS

Tegaserod Maleate Suppresses the Growth of Gastric Cancer In Vivo and In Vitro by Targeting MEK1/2. (PubMed, Cancers (Basel)) - "We further compared the effect between tegaserod maleate and trametinib, which is a clinical MEK1/2 inhibitor, and confirmed that tegaserod maleate has the same effect as trametinib in inhibiting the growth of GC. Our findings suggest that tegaserod maleate inhibited GC proliferation by targeting MEK1/2."

Journal • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MAP2K1

Hydrogen Bonding Penalty Used for Virtual Screening to Discover Potent Inhibitors for Papain-Like Cysteine Proteases of SARS-CoV-2. (PubMed, Chem Biol Drug Des) - "Finally, 61 compounds were acquired and 4 of them with IC at micromolar level tested in vitro enzyme activity assay, which include clinical drugs tegaserod...The binding modes of these 4 compounds were further explored with metadynamics simulations. The hits will provide a starting point for future key interactions identified and lead optimisation targetting PLpro."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Constipation. (PubMed, Gastroenterology) - "The panel agreed on 9 recommendations for the management of patients with IBS-C. The panel made a strong recommendation for linaclotide (high certainty) and conditional recommendations for tenapanor, plecanatide, tegaserod, and lubiprostone (moderate certainty), polyethylene glycol laxatives, tricyclic antidepressants, and antispasmodics (low certainty). The panel made a conditional recommendation against the use of selective serotonin reuptake inhibitors (low certainty)."

Clinical guideline • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology

Tenapanor (Ibsrela) for irritable bowel syndrome with constipation. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology

Real-World Treatment Strategies to Improve Outcomes in Patients With Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation. (PubMed, Am J Gastroenterol) - "When these options fail, prescription secretagogues (plecanatide, linaclotide, lubiprostone, and tenapanor [pending commercial availability]), or serotonergic agents (prucalopride and tegaserod) are generally preferred. Given the broad spectrum of available agents, therapy should be tailored by mutual decision-making between the patient and practitioner. Overall, patients need to be actively monitored and managed to maximize clinical outcomes."

HEOR • Journal • Real-world evidence • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology • Pain

Tegaserod Maleate Inhibits Breast Cancer Progression and Enhances the Sensitivity of Immunotherapy. (PubMed, J Oncol) - "Moreover, the combination of anti-TIGIT and TM has the best inhibitory effect. TM inhibited the progression of breast cancer, and its combination with anti-TIGIT could effectively inhibit tumor growth and improve the sensitivity of immunotherapy in breast cancer."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • TIGIT

TEGASEROD: WHAT'S OLD IS NEW AGAIN. (PubMed, Clin Gastroenterol Hepatol) - "This review summarizes the regulatory journey of tegaserod, and details the existing pharmacokinetic, physiologic, clinical, and safety data of tegaserod generated over the last two decades. The discussion also examines the future of tegaserod in the treatment of these constipation disorders, as well as its potential role in other related disorders of brain-gut interaction (DGBI)."

Journal • Review • Cardiovascular • CNS Disorders • Constipation • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Immunology

"Yeah its stupid to ask questions I assume you are still using Asbestos in your home? Imagine if you couldnt question the effects of Zomepirac, Valdecoxib, Thioridazine or Tegaserod. I mean you cant question the science and these all passed safety checks and was approved for use." (@TyTalksTechblog)

Clinical

Review article: current and future treatment approaches for IBS with constipation. (PubMed, Aliment Pharmacol Ther) - "Quality of life and symptom metrics should be standardized and continue to be represented in future IBS-C trials. The choice of agent should be tailored to probability of improving symptoms, safety, tolerability, and cost."

Journal • Review • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology

Diarrhea-Predominant and Constipation-Predominant Irritable Bowel Syndrome: Current Prescription Drug Treatment Options. (PubMed, Drugs) - "We performed a narrative review of the literature to summarize these important determinants of treatment choice including: labeled indications; clinical profiles of efficacy, safety, and tolerability of prescription drugs; and cost-effectiveness for diarrhea-predominant IBS drugs (IBS-D: alosetron, eluxadoline, and rifaximin) and constipation-predominant IBS drugs (IBS-C: linaclotide, lubiprostone, plecanatide, tegaserod, and tenapanor). We then review the standard model of shared decision-making aimed at guiding an informed, patient-centered discussion to integrate comparative clinical and cost outcomes toward choosing an IBS treatment in practice."

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology

Active Targeted Nanoemulsions for Repurposing of Tegaserod in Alzheimer's Disease Treatment. (PubMed, Pharmaceutics) - "The developed peptide-22 functionalized Tg-NEs appear as a valuable tool to allow exploration of the repurposed tegaserod in AD treatment in further preclinical studies."

Journal • Alzheimer's Disease • CNS Disorders • Gastrointestinal Disorder • Immunology

"✳️IBS-D: Rifaximin; Eluxadoline (C/I: CCY, EtOH, pancreatitis, SOD, liver disease) ✳️IBS-C: GC-C agonist; Tegaserod (5HT4 agonist) for 🚺 <65 with <1 CV factor #ACG2021 #ItsComplicated" (@doctornikkid)

Hepatology • Pancreatitis