Tegaserod
Identification
- Summary
Tegaserod is a serotonin-4 (5-HT4) receptor agonist indicated for the treatment of constipation predominant irritable bowel syndrome (IBS-C) specifically in women under the age of 65. There is currently no safety or efficacy data for use of tegaserol in men.
- Brand Names
- Zelnorm
- Generic Name
- Tegaserod
- DrugBank Accession Number
- DB01079
- Background
Novartis' brand name Zelnorm (tegaserod) had originally received approval from the US FDA in 2002 for the treatment of irritable bowel syndrome with constipation (IBS-C).5,8 It was, however, voluntarily withdrawn from widespread use in the US market in 2007 after concerns arose over the possibility that tegaserod could potentially cause dangerous cardiovascular events in patients.5,8 Since then, closer evaluations of the original data suggesting such cardiovascular risk have resulted in the limited reintroduction or 're-approval' of tegaserod for treatment of IBS-C specifically in female patients less than 65 years of age and whom are considered to be at a lower risk of a cardiovascular event than the broader population.5,8 Zelnorm (tegaserod) by Sloan Pharma subsequently gained re-approval in April of 2019.5 Nevertheless, tegaserod remains un-approved in certain regions.7
Despite the relative complications involved in its history of regulatory approval, ever since its first introduction in 2002 tegaserod remains the only therapy for IBS-C that possesses the unique mechanism of action of acting on serotonin-4 (5-HT(4)) receptors in smooth muscle cells and in the gastrointestinal wall to facilitate actions like esophageal relaxation, peristaltic gut movement, and natural secretions in the gut, among others.5,1,3,8,6
- Type
- Small Molecule
- Groups
- Approved, Investigational, Withdrawn
- Structure
- Weight
- Average: 301.394
Monoisotopic: 301.190260381 - Chemical Formula
- C16H23N5O
- Synonyms
- 1-(((5-Methoxyindol-3-yl)methylene)amino)-3-pentylguanidine
- Tégasérod
- Tegaserod
- Tegaserodum
- External IDs
- HTF 919
- HTF-919
- SDZ HTF 919
- SDZ-HTF-919
Pharmacology
- Indication
Tegaserod is a serotonin-4 (5-HT4) receptor agonist indicated for the treatment of adult women less than 65 years of age with irritable bowel syndrome with constipation (IBS-C) 6,8. The safety and effectiveness of tegaserod in men with IBS-C have not been established 6,8.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Irritable bowel syndrome with constipation (ibs-c) •••••••••••• ••••• •••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
In general, it has been determined that tegaserod is an agonist of serotonin type-4 (5-HT(4)) receptors, an antagonist at 5-HT(2B) receptors, but is expected to possess minimal binding to 5-HT(1) receptors, and virtually no affinity for 5-HT(3) or dopamine receptors 1,3,6.
In clinical trials with tegaserod, centrally analyzed ECGs were recorded in 4,605 male and female patients receiving tegaserod 6 mg twice daily or placebo for IBS-C and other related motility disorders 6,8. No subject receiving the agent had an absolute QTcF above 480 ms 6,8. An increase in QTcF of 30 to 60 ms was observed in 7% of patients receiving tegaserod and 8% receiving placebo 6,8. An increase in QTcF of greater than 60 ms was observed in 0.3% and 0.2% of subjects, respectively 6,8. The effects of tegaserod on the QTcF interval were ultimately not considered to be clinically meaningful 6,8.
Furthermore, it was determined that there is a potential for tegaserod and its main metabolite (the M29 metabolite) to increase platelet aggregation in vitro 6,8. In one in vitro study, at concentrations up to 10-times the maximum plasma concentration (Cmax) at the recommended dose, tegaserod significantly increased platelet aggregation in a concentration-dependent manner up to 74% (range 11% to 74%) compared to a control vehicle (with potentiation by various agonists) 6,8. In another in vitro study, the M29 metabolite, at concentrations up to 0.6-times the Cmax of M29 also showed a 5% to 16% increase in platelet aggregation compared to the control vehicle 6,8. The clinical implications of these in vitro platelet aggregation results remain unclear 6,8.
- Mechanism of action
Irritable bowel syndrome (IBS) is a complex functional disorder comprised of various abnormal and discomforting effects on the gastrointestinal tract and bowel function 2,6,7,8. Although the cause of IBS has yet to be formally elucidated, patient experience has demonstrated that the disorder is typically associated with abdominal pain, abdominal distension, cramping or bloating, variations in urgency for bowel movements, feelings of incomplete evacuation, gastroesophageal reflux, and various other effects 2,6,7,8. In particular, IBS that features constipation as a predominant effect is categorized as constipation-predominant IBS, or IBS-C 6,8.
Concurrently, 5-Hydroxytryptamine (5-HT, or serotonin) has demonstrated the ability to elicit significant regulatory actions on gastrointestinal motility 1. Specifically, it has been shown that the activation of 5-HT(4) receptors located on motor neurons and interneurons in the gastrointestinal wall can cause the release of acetylcholine, substance P, and calcitonin gene-related peptide that can all facilitate the propulsion of material through the gut 1. Moreover, when 5-HT(4) receptors located in smooth muscle cells are also activated, activities that may alleviate symptoms of IBS-C like esophageal relaxation and the inhibition of human colonic circular muscle contraction can also occur 1. Additionally, activating 5-HT(4) on enteric neurons and enterocytes also cause natural fluid secretion in the gut - an action which also strongly assists in promoting the movement of content along the gastrointestinal tract 1.
Alternatively, it has also been observed that 5-HT may participate in generating visceral hyperalgesia in IBS, an observation supported in part by the finding of increased amounts of 5-HT and its metabolites in the plasma of patients experiencing IBS 3 It has therefore also been proposed that antagonism of 5-HT(2B) receptors can lead to inhibition of both 5-HT mediated gastrointestinal motility and visceral hypersensitivity 1.
Subsequently, because tegaserod is considered to be an agonist of the 5-HT(4) receptor and an antagonist of the 5-HT(2B) receptor at clinically relevant levels, it is believed that tegaserod may elicit its mechanism of action by facilitating activities associated with the activation and antagonism of the 5-HT(4) and 5-HT(2B) receptors, like stimulating peristaltic gastrointestinal reflexes and intestinal secretion, inhibiting visceral sensitivity, enhancing basal motor activity, and normalizing impaired motility throughout the gastrointestinal tract, among other actions 1,3,6,7,8.
Target Actions Organism A5-hydroxytryptamine receptor 4 antagonistpartial agonistHumans U5-hydroxytryptamine receptor 2C antagonistHumans U5-hydroxytryptamine receptor 2A antagonistHumans U5-hydroxytryptamine receptor 2B antagonistHumans - Absorption
The absolute bioavailability of tegaserod is approximately 10% when administered to fasting subjects. The median time of peak tegaserod plasma concentration (Tmax) is approximately one hour (range 0.7 to 2 hours) 6.
Nevertheless, when tegaserod was given to individuals thirty minutes before a meal of high-fat and high-calorie content (about 150 calories from protein, 250 calories from carbohydrates, and 500 calories from fat), the AUC was reduced by 40% to 65%, the Cmax was reduced by approximately 20% to 40%, and the median Tmax was 0.7 hours 6. Additionally, plasma concentrations were similar when tegaserod was administered within thirty minutes before a meal or even two and a half hours after a meal 6.
- Volume of distribution
Although tegaserod is not approved for intravenous administration, data regarding the mean volume of distribution of tegaserod at steady-state is recorded as 368 ± 223 L following research of tegaserod administered intravenously 6.
- Protein binding
The protein binding recorded for tegaserod is about 98% 6.
- Metabolism
Tegaserod is ultimately metabolized by way of hydrolysis and direct glucuronidation 6,4. The substance is firstly hydrolyzed in the stomach 6,4. It then undergoes oxidization and then conjugation to produce the main circulating tegaserod metabolite in human plasma, the so-called M29 metabolite, or 5-methoxyindole-3-carboxylic acid 6,4. Nevertheless, it has been determined that this main circulating metabolite has negligible affinity for 5-HT(4) receptors in vitro 6,4. Furthermore, tegaserod can also experience direct N-glucuronidation at each of its three guanidine nitrogens which leads to the generation of three isomeric N-glucuronides - the so-called M43.2, M43.8, and M45.3 metabolites 4.
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- Route of elimination
Approximately two-thirds of an orally administered dose of tegaserod is excreted unchanged in the feces, with the remaining one-third excreted in the urine as metabolites 6.
- Half-life
The mean terminal elimination half-life documented for tegaserod ranges from 4.6 to 8.1 hours following oral administration 6.
- Clearance
Although tegaserod is not approved for intravenous administration, data regarding the mean plasma clearance of tegaserod is documented as 77 ± 15 L/h following research of tegaserod administered intravenously 6.
- Adverse Effects
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- Toxicity
Single oral doses of 120 mg (which is 20 times the recommended dose) of tegaserod were administered to three healthy subjects in one study 6. All three subjects developed diarrhea and headache. Two of these subjects also reported intermittent abdominal pain and one developed orthostatic hypotension 6. In 28 healthy subjects exposed to 90 to 180 mg per day of tegaserod (which is 7.5 to 15 times the recommended daily dosage) for several days, adverse reactions were diarrhea (100%), headache (57%), abdominal pain (18%), flatulence (18%), nausea (7%), and vomiting (7%) 6.
Although available data from case reports with tegaserod use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, animal studies involving maternal dietary administration of tegaserod with doses 45 to 71 times the recommended dose demonstrated decreased body weight, delays in developmental landmarks, and decreased survival in rat pups 6. Caution and careful consideration of risks versus benefits are recommended before administering tegaserod to a pregnant woman.
Despite there being little if any data available regarding the presence of tegaserod in human milk, the effects on the breastfed infant, or the effects on milk production, tegaserod and its metabolites are present in rat milk and the milk to plasma concentration ratio is very high in rats 6. Subsequently, because of the potential for serious reactions in the breastfed infant, including tumorigenicity, breastfeeding is not recommended during treatment with tegaserod 6.
The safety and effectiveness of tegaserod in pediatric patients has not yet been established 6.
Tegaserod is not indicated in patients that are aged 65 years or older 6.
Tegaserod was not carcinogenic in rats given oral dietary doses up to 180 mg/kg/day (approximately 93 to 111 times the recommended dose based on AUC) for 110 to 124 weeks 6. In mice, dietary administration of tegaserod for 104 weeks produced mucosal hyperplasia and adenocarcinoma of the small intestine at 600 mg/kg/day (approximately 83 to 110 times the recommended dose based on AUC) 6. There was no evidence of carcinogenicity at lower doses (3 to 35 times the recommended dose based on AUC) 6. Tegaserod was not genotoxic in the in vitro Chinese hamster lung fibroblast (CHL/V79) cell chromosomal aberration and forward mutation test, the in vitro rat hepatocyte unscheduled DNA synthesis (UDS) test or the in vivo mouse micronucleus test 6. The results of the Ames test for mutagenicity were equivocal. Tegaserod at oral (dietary) doses up to 240 mg/kg/day (approximately 57 times the recommended dose based on AUC) in male rats and 150 mg/kg/day (approximately 42 times the recommended dose based on AUC) in female rats was found to have no effect on fertility and reproductive performance 6.
Inhibition of the hERG (human Ether-a-go-go-Related Gene) channel was evident only in the micromolar concentration range with an IC50 of 13 micromolar (approximately 1300 times the Cmax in humans at the recommended dose) 6. In in vitro studies, tegaserod had no effects on impulse conduction in isolated guinea pig papillary muscle at up to 100 times the Cmax in humans, Langendorff-perfused isolated rabbit heart (QT interval) at up to 1000 times the Cmax in humans, or human atrial myocytes at multiples up to 10 times the Cmax in humans 6. The major metabolite, M29, had no effect on QT in the Langendorff-perfused isolated rabbit heart at multiples up to 323 times the Cmax in humans 6.
In anesthetized and conscious dogs, tegaserod at doses up to 92 to 134 times the recommended dose based on Cmax did not alter heart rate, QRS interval duration, QTc or other ECG parameters 6. In chronic toxicology studies in rats and dogs, there were no treatment-related changes in cardiac morphology after tegaserod administration at doses up to 660 times the recommended dose based on AUC 6.
Although tegaserod is expected to bind to 5-HT2B receptors in humans at the recommended dose, there does not appear to be any potential for heart valve injury based on functional evidence of 5-HT2B receptor antagonism 6.
Studies with isolated coronary and mesenteric blood vessels from non-human primates and humans showed no vasoconstrictor effect at concentrations approximately 100 times the human Cmax 6. Tegaserod exhibited antagonism of 5-HT-mediated vasoconstriction via 5-HT1B receptors 6. In rat thoracic aortic rings that were pre-constricted with phenylephrine or norepinephrine, tegaserod produced vasorelaxation, with IC50 values 6 and 64 times the Cmax plasma concentrations in humans, respectively 6. No effects were observed in the basal tone of aortic rings at concentrations up to 1000 times the human Cmax 6.
In studies with an anesthetized rat model for measuring macro- and micro-circulation of the colon, intraduodenal dosing with tegaserod (approximately 7 times the recommended dose based on Cmax) produced no clinically relevant effect on blood pressure, heart rate, or vascular conductance 6.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The metabolism of Tegaserod can be increased when combined with Abatacept. Abemaciclib Abemaciclib may decrease the excretion rate of Tegaserod which could result in a higher serum level. Abiraterone The metabolism of Tegaserod can be decreased when combined with Abiraterone. Abrocitinib The serum concentration of Tegaserod can be increased when it is combined with Abrocitinib. Acebutolol The metabolism of Acebutolol can be decreased when combined with Tegaserod. - Food Interactions
- Take before a meal. To increase absorption, take 30 minutes before a meal.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Tegaserod maleate E5XNT3RF5A 189188-57-6 CPDDZSSEAVLMRY-FEQFWAPWSA-N - International/Other Brands
- Zelmac
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Zelnorm Tablet 2 mg/1 Oral Novartis 2002-07-24 2010-05-31 US Zelnorm Tablet 6 mg/1 Oral Novartis 2002-07-24 2009-01-31 US Zelnorm Tablet 6 mg/1 Oral Alfasigma USA, Inc. 2019-08-01 Not applicable US Zelnorm Tablet 6 mg/1 Oral Novartis 2002-07-24 2008-06-30 US Zelnorm Tablet 6 mg/1 Oral US WorldMeds, LLC 2019-07-29 2022-08-31 US
Categories
- ATC Codes
- A06AX06 — Tegaserod
- Drug Categories
- Alimentary Tract and Metabolism
- Antidepressive Agents
- BCRP/ABCG2 Substrates
- Central Nervous System Depressants
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (weak)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (moderate)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2E1 Inhibitors
- Cytochrome P-450 CYP2E1 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs for Constipation
- Gastrointestinal Agents
- Heterocyclic Compounds, Fused-Ring
- Laxatives
- P-glycoprotein substrates
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin 4 Receptor Agonists
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2A Receptor Antagonists
- Serotonin 5-HT2C Receptor Antagonists
- Serotonin Agents
- Serotonin Receptor Antagonists
- Serotonin-4 Receptor Agonist
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as indoles. These are compounds containing an indole moiety, which consists of pyrrole ring fused to benzene to form 2,3-benzopyrrole.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Indoles
- Direct Parent
- Indoles
- Alternative Parents
- Anisoles / Alkyl aryl ethers / Substituted pyrroles / Heteroaromatic compounds / Guanidines / Carboximidamides / Azacyclic compounds / Organopnictogen compounds / Imines / Hydrocarbon derivatives
- Substituents
- Alkyl aryl ether / Anisole / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carboximidamide / Ether / Guanidine / Heteroaromatic compound / Hydrocarbon derivative
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- guanidines, indoles, carboxamidine, hydrazines (CHEBI:51043)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 458VC51857
- CAS number
- 145158-71-0
- InChI Key
- IKBKZGMPCYNSLU-RGVLZGJSSA-N
- InChI
- InChI=1S/C16H23N5O/c1-3-4-5-8-18-16(17)21-20-11-12-10-19-15-7-6-13(22-2)9-14(12)15/h6-7,9-11,19H,3-5,8H2,1-2H3,(H3,17,18,21)/b20-11+
- IUPAC Name
- N'-[(E)-[(5-methoxy-1H-indol-3-yl)methylidene]amino]-N-pentylguanidine
- SMILES
- CCCCCNC(=N)N\N=C\C1=CNC2=C1C=C(OC)C=C2
References
- Synthesis Reference
Sundaram Venkataraman, Srinivasulu Gudipati, Brahmeshwararao Mandava Venkata Naga, Goverdhan Banda, Radhakrishna Singamsetty, "Process for preparing form I of tegaserod maleate." U.S. Patent US20050272802, issued December 08, 2005.
US20050272802- General References
- Beattie DT, Smith JA, Marquess D, Vickery RG, Armstrong SR, Pulido-Rios T, McCullough JL, Sandlund C, Richardson C, Mai N, Humphrey PP: The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo. Br J Pharmacol. 2004 Nov;143(5):549-60. Epub 2004 Oct 4. [Article]
- Talley NJ: Irritable bowel syndrome. Intern Med J. 2006 Nov;36(11):724-8. doi: 10.1111/j.1445-5994.2006.01217.x. [Article]
- Borman RA, Tilford NS, Harmer DW, Day N, Ellis ES, Sheldrick RL, Carey J, Coleman RA, Baxter GS: 5-HT(2B) receptors play a key role in mediating the excitatory effects of 5-HT in human colon in vitro. Br J Pharmacol. 2002 Mar;135(5):1144-51. doi: 10.1038/sj.bjp.0704571. [Article]
- Vickers AE, Zollinger M, Dannecker R, Tynes R, Heitz F, Fischer V: In vitro metabolism of tegaserod in human liver and intestine: assessment of drug interactions. Drug Metab Dispos. 2001 Oct;29(10):1269-76. [Article]
- FDA approves the reintroduction of Zelnorm™ (tegaserod) for Irritable Bowel Syndrome with Constipation (IBS-C) in women under 65 [Link]
- Tegaserod 2019 FDA Label [File]
- EMA Refusal Assessment Report for Zelnorm (Tegaserod) [File]
- FDA Joint Meeting of the Gastrointestinal Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee Briefing Document for Zelnorm (tegaserod maleate) [File]
- External Links
- KEGG Drug
- D06056
- PubChem Compound
- 5362436
- PubChem Substance
- 46506519
- ChemSpider
- 10609889
- BindingDB
- 79022
- 139778
- ChEBI
- 51043
- ChEMBL
- CHEMBL76370
- ZINC
- ZINC000001545565
- Therapeutic Targets Database
- DAP001526
- PharmGKB
- PA130413154
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Tegaserod
- FDA label
- Download (634 KB)
- MSDS
- Download (58.1 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Chronic Constipation 1 4 Completed Treatment Constipation 1 4 Completed Treatment IBS-C and IBS With Mixed Bowel Habits 1 4 Terminated Treatment Chronic Constipation 1 4 Terminated Treatment Diabetes / Gastroparesis 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Murfreesboro Pharmaceutical Nursing Supply
- Novartis AG
- Dosage Forms
Form Route Strength Tablet Oral 2 mg/1 Tablet Oral 6 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5510353 No 1996-04-23 2013-04-26 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 155 °C Not Available logP 2.6 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0288 mg/mL ALOGPS logP 2.76 ALOGPS logP 2.95 Chemaxon logS -4 ALOGPS pKa (Strongest Acidic) 15.24 Chemaxon pKa (Strongest Basic) 8.5 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 85.29 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 110.25 m3·mol-1 Chemaxon Polarizability 34.96 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9973 Blood Brain Barrier + 0.7842 Caco-2 permeable - 0.5939 P-glycoprotein substrate Substrate 0.921 P-glycoprotein inhibitor I Non-inhibitor 0.8978 P-glycoprotein inhibitor II Non-inhibitor 0.959 Renal organic cation transporter Inhibitor 0.5488 CYP450 2C9 substrate Non-substrate 0.8522 CYP450 2D6 substrate Non-substrate 0.5492 CYP450 3A4 substrate Non-substrate 0.6565 CYP450 1A2 substrate Non-inhibitor 0.53 CYP450 2C9 inhibitor Non-inhibitor 0.7096 CYP450 2D6 inhibitor Non-inhibitor 0.7807 CYP450 2C19 inhibitor Non-inhibitor 0.6372 CYP450 3A4 inhibitor Non-inhibitor 0.8954 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7654 Ames test Non AMES toxic 0.5434 Carcinogenicity Non-carcinogens 0.7783 Biodegradation Not ready biodegradable 0.9972 Rat acute toxicity 2.6038 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.5123 hERG inhibition (predictor II) Non-inhibitor 0.8334
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0596-1901000000-b5deee1659020a91be3f Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-0009000000-bcf39279c6c90371f51b Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-05fu-2900000000-f9bb84c106bb7727169c Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0fk9-9735000000-d4de4cd093952c31c17b Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-1900000000-7b5a50f90138f090f4eb Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00dl-4900000000-3d948d19ce7fc62989a5 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 184.3702351 predictedDarkChem Lite v0.1.0 [M-H]- 174.32275 predictedDeepCCS 1.0 (2019) [M+H]+ 185.3474351 predictedDarkChem Lite v0.1.0 [M+H]+ 176.68074 predictedDeepCCS 1.0 (2019) [M+Na]+ 185.0795351 predictedDarkChem Lite v0.1.0 [M+Na]+ 182.77391 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistPartial agonist
- General Function
- Serotonin receptor activity
- Specific Function
- This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
- Gene Name
- HTR4
- Uniprot ID
- Q13639
- Uniprot Name
- 5-hydroxytryptamine receptor 4
- Molecular Weight
- 43760.975 Da
References
- Camilleri M: Review article: tegaserod. Aliment Pharmacol Ther. 2001 Mar;15(3):277-89. [Article]
- Kamm MA: Review article: the complexity of drug development for irritable bowel syndrome. Aliment Pharmacol Ther. 2002 Mar;16(3):343-51. [Article]
- Corsetti M, Tack J: Tegaserod: a new 5-HT(4) agonist in the treatment of irritable bowel syndrome. Expert Opin Pharmacother. 2002 Aug;3(8):1211-8. [Article]
- Beattie DT, Smith JA, Marquess D, Vickery RG, Armstrong SR, Pulido-Rios T, McCullough JL, Sandlund C, Richardson C, Mai N, Humphrey PP: The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo. Br J Pharmacol. 2004 Nov;143(5):549-60. Epub 2004 Oct 4. [Article]
- Cole P, Rabasseda X: Tegaserod: a serotonin 5-HT4 receptor agonist for treatment of constipation-predominant irritable bowel syndrome. Drugs Today (Barc). 2004 Dec;40(12):1013-30. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Serotonin receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
- Gene Name
- HTR2C
- Uniprot ID
- P28335
- Uniprot Name
- 5-hydroxytryptamine receptor 2C
- Molecular Weight
- 51820.705 Da
References
- Beattie DT, Smith JA, Marquess D, Vickery RG, Armstrong SR, Pulido-Rios T, McCullough JL, Sandlund C, Richardson C, Mai N, Humphrey PP: The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo. Br J Pharmacol. 2004 Nov;143(5):549-60. Epub 2004 Oct 4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Virus receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
- Gene Name
- HTR2A
- Uniprot ID
- P28223
- Uniprot Name
- 5-hydroxytryptamine receptor 2A
- Molecular Weight
- 52602.58 Da
References
- Beattie DT, Smith JA, Marquess D, Vickery RG, Armstrong SR, Pulido-Rios T, McCullough JL, Sandlund C, Richardson C, Mai N, Humphrey PP: The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo. Br J Pharmacol. 2004 Nov;143(5):549-60. Epub 2004 Oct 4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Serotonin receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
- Gene Name
- HTR2B
- Uniprot ID
- P41595
- Uniprot Name
- 5-hydroxytryptamine receptor 2B
- Molecular Weight
- 54297.41 Da
References
- Beattie DT, Smith JA, Marquess D, Vickery RG, Armstrong SR, Pulido-Rios T, McCullough JL, Sandlund C, Richardson C, Mai N, Humphrey PP: The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo. Br J Pharmacol. 2004 Nov;143(5):549-60. Epub 2004 Oct 4. [Article]
- McCullough JL, Armstrong SR, Hegde SS, Beattie DT: The 5-HT2B antagonist and 5-HT4 agonist activities of tegaserod in the anaesthetized rat. Pharmacol Res. 2006 Apr;53(4):353-8. Epub 2006 Feb 21. [Article]
- Greenwood-Van Meerveld B, Campbell-Dittmeyer K, Johnson AC, Hicks GA: 5-HT2B receptors do not modulate sensitivity to colonic distension in rats with acute colorectal hypersensitivity. Neurogastroenterol Motil. 2006 May;18(5):343-5. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Zhou H, Khalilieh S, Svendsen K, Pommier F, Osborne S, Appel-Dingemanse S, Lasseter K, McLeod JF: Tegaserod coadministration does not alter the pharmacokinetics of theophylline in healthy subjects. J Clin Pharmacol. 2001 Sep;41(9):987-93. [Article]
- Vickers AE, Zollinger M, Dannecker R, Tynes R, Heitz F, Fischer V: In vitro metabolism of tegaserod in human liver and intestine: assessment of drug interactions. Drug Metab Dispos. 2001 Oct;29(10):1269-76. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [Article]
- Vickers AE, Zollinger M, Dannecker R, Tynes R, Heitz F, Fischer V: In vitro metabolism of tegaserod in human liver and intestine: assessment of drug interactions. Drug Metab Dispos. 2001 Oct;29(10):1269-76. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Vickers AE, Zollinger M, Dannecker R, Tynes R, Heitz F, Fischer V: In vitro metabolism of tegaserod in human liver and intestine: assessment of drug interactions. Drug Metab Dispos. 2001 Oct;29(10):1269-76. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Vickers AE, Zollinger M, Dannecker R, Tynes R, Heitz F, Fischer V: In vitro metabolism of tegaserod in human liver and intestine: assessment of drug interactions. Drug Metab Dispos. 2001 Oct;29(10):1269-76. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Serotonin:sodium symporter activity
- Specific Function
- Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
- Gene Name
- SLC6A4
- Uniprot ID
- P31645
- Uniprot Name
- Sodium-dependent serotonin transporter
- Molecular Weight
- 70324.165 Da
References
- Ismair MG, Kullak-Ublick GA, Blakely RD, Fried M, Vavricka SR: Tegaserod inhibits the serotonin transporter SERT. Digestion. 2007;75(2-3):90-5. Epub 2007 May 18. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
References
- Tegaserod 2019 FDA Label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Tegaserod 2019 FDA Label [File]
Drug created at June 13, 2005 13:24 / Updated at May 07, 2021 21:22