Identification

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Name
Tegaserod
Accession Number
DB01079  (APRD00096)
Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Description

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 It was, however, voluntarily withdrawn from widespread use in the US market in 2007 after concerns arose over the possibility that tegaserod could potentially cause dangerous cardiovascular events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.

Structure
Thumb
Synonyms
  • 1-(((5-Methoxyindol-3-yl)methylene)amino)-3-pentylguanidine
  • Tegaserod
  • Tégasérod
  • Tegaserodum
External IDs
HTF 919 / HTF-919 / SDZ HTF 919 / SDZ-HTF-919
Product Ingredients
IngredientUNIICASInChI Key
Tegaserod maleateE5XNT3RF5A189188-57-6CPDDZSSEAVLMRY-FEQFWAPWSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ZelnormTablet6 mg/1OralNovartis2002-07-242008-06-30Us
ZelnormTablet2 mg/1OralNovartis2002-07-242010-05-31Us
ZelnormTablet6 mg/1OralAlfasigma USA, Inc.2019-08-01Not applicableUs
ZelnormTablet6 mg/1OralUS WorldMeds, LLC2019-07-29Not applicableUs
ZelnormTablet6 mg/1OralNovartis2002-07-242009-01-31Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Zelmac
Categories
UNII
458VC51857
CAS number
145158-71-0
Weight
Average: 301.394
Monoisotopic: 301.190260381
Chemical Formula
C16H23N5O
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

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.

Associated Conditions
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.

TargetActionsOrganism
A5-hydroxytryptamine receptor 4
antagonist
partial agonist
Humans
U5-hydroxytryptamine receptor 2B
antagonist
Humans
U5-hydroxytryptamine receptor 2C
antagonist
Humans
U5-hydroxytryptamine receptor 2A
antagonist
Humans
Additional Data Available
Adverse Effects

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Contraindications

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Blackbox Warnings

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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.

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.

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.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Tegaserod.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Tegaserod.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidineThe metabolism of Tegaserod can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Tegaserod is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Tegaserod is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when Tegaserod is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Tegaserod.
5-methoxy-N,N-dimethyltryptamineThe metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Tegaserod.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Tegaserod.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of serotonin syndrome can be increased when Tegaserod is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
  • Take before a meal, to increase absorption, take 30 minutes before a meal.

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
  1. 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. [PubMed:15466450]
  2. Talley NJ: Irritable bowel syndrome. Intern Med J. 2006 Nov;36(11):724-8. doi: 10.1111/j.1445-5994.2006.01217.x. [PubMed:17040359]
  3. 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. [PubMed:11877320]
  4. 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. [PubMed:11560869]
  5. FDA approves the reintroduction of Zelnorm™ (tegaserod) for Irritable Bowel Syndrome with Constipation (IBS-C) in women under 65 [Link]
  6. Tegaserod 2019 FDA Label [File]
  7. EMA Refusal Assessment Report for Zelnorm (Tegaserod) [File]
  8. 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
ChEBI
51043
ChEMBL
CHEMBL76370
Therapeutic Targets Database
DAP001526
PharmGKB
PA130413154
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tegaserod
ATC Codes
A06AX06 — Tegaserod
FDA label
Download (634 KB)
MSDS
Download (58.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentSymptomatic Gastroespohageal Reflux Disease1
2TerminatedNot AvailableDiabetic Gastropathy1
2, 3TerminatedTreatmentConstipation1
3CompletedTreatmentChronic Constipation1
3CompletedTreatmentConstipation1
3CompletedTreatmentDyspepsia5
3CompletedTreatmentDyspepsia / Heartburn1
3CompletedTreatmentGastro-esophageal Reflux Disease (GERD)2
3TerminatedTreatmentConstipation Predominant / Irritable Bowel Syndrome (IBS-C)1
3TerminatedTreatmentOpioid Induced Constipation (OIC)2
4CompletedTreatmentChronic Constipation1
4CompletedTreatmentConstipation1
4CompletedTreatmentIBS-C and IBS With Mixed Bowel Habits1
4TerminatedTreatmentChronic Constipation1
4TerminatedTreatmentDiabetes Mellitus (DM) / Gastroparesis1
Not AvailableNo Longer AvailableNot AvailableChronic Idiopathic Constipation / Constipation-predominant Irritable Bowel Syndrome (IBS-C)1
Not AvailableTerminatedTreatmentConstipation / Disease, Chronic1
Not AvailableUnknown StatusTreatmentConstipation1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Murfreesboro Pharmaceutical Nursing Supply
  • Novartis AG
Dosage forms
FormRouteStrength
TabletOral2 mg/1
TabletOral6 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5510353No1996-04-232013-04-26Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)155 °CNot Available
logP2.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0288 mg/mLALOGPS
logP2.76ALOGPS
logP2.95ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)15.24ChemAxon
pKa (Strongest Basic)8.5ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area85.29 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity110.25 m3·mol-1ChemAxon
Polarizability34.96 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9973
Blood Brain Barrier+0.7842
Caco-2 permeable-0.5939
P-glycoprotein substrateSubstrate0.921
P-glycoprotein inhibitor INon-inhibitor0.8978
P-glycoprotein inhibitor IINon-inhibitor0.959
Renal organic cation transporterInhibitor0.5488
CYP450 2C9 substrateNon-substrate0.8522
CYP450 2D6 substrateNon-substrate0.5492
CYP450 3A4 substrateNon-substrate0.6565
CYP450 1A2 substrateNon-inhibitor0.53
CYP450 2C9 inhibitorNon-inhibitor0.7096
CYP450 2D6 inhibitorNon-inhibitor0.7807
CYP450 2C19 inhibitorNon-inhibitor0.6372
CYP450 3A4 inhibitorNon-inhibitor0.8954
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7654
Ames testNon AMES toxic0.5434
CarcinogenicityNon-carcinogens0.7783
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity2.6038 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5123
hERG inhibition (predictor II)Non-inhibitor0.8334
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Indole / Anisole / Alkyl aryl ether / Substituted pyrrole / Benzenoid / Pyrrole / Heteroaromatic compound / Guanidine / Azacycle / Ether
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
guanidines, indoles, carboxamidine, hydrazines (CHEBI:51043)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
Partial 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
  1. Camilleri M: Review article: tegaserod. Aliment Pharmacol Ther. 2001 Mar;15(3):277-89. [PubMed:11207504]
  2. Kamm MA: Review article: the complexity of drug development for irritable bowel syndrome. Aliment Pharmacol Ther. 2002 Mar;16(3):343-51. [PubMed:11876686]
  3. 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. [PubMed:12150698]
  4. 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. [PubMed:15466450]
  5. 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. [PubMed:15645012]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
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
  1. 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. [PubMed:15466450]
  2. 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. [PubMed:16495076]
  3. 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. [PubMed:16629860]
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
  1. 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. [PubMed:15466450]
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
  1. 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. [PubMed:15466450]

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
  1. 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. [PubMed:11549104]
  2. 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. [PubMed:11560869]
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
  1. 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. [PubMed:26721703]
  2. 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. [PubMed:11560869]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. 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. [PubMed:11560869]
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
  1. 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. [PubMed:11560869]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. 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. [PubMed:17510552]
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
  1. 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
  1. Tegaserod 2019 FDA Label [File]

Drug created on June 13, 2005 07:24 / Updated on December 02, 2019 05:42