General
Preferred name
TEGASEROD
Synonyms
TEGASEROD MALEATE ()
HTF-919 ()
SDZ-HTF-919 ()
Tegaserod (maleate) ()
Zelmac ()
Zelnorm ()
HTF 919 ()
NSC-760425 ()
P&D ID
PD013069
CAS
145158-71-0
189188-57-6
Tags
natural product
drug
available
Drug Status
investigational
approved
withdrawn
Drug indication
Dyspepsia
Irritable bowel syndrome
Gastro-oesophageal reflux
Max Phase
Phase 4
First approval
2002
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE The mean terminal elimination half-life documented for tegaserod ranges from 4.6 to 8.1 hours following oral administration [F4223].
ROE 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 [F4223].
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) [F4223, F4229]. The safety and effectiveness of tegaserod in men with IBS-C have not been established [F4223, F4229].
METABOLISM Tegaserod is ultimately metabolized by way of hydrolysis and direct glucuronidation [F4223, A38972]. The substance is firstly hydrolyzed in the stomach [F4223, A38972]. 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 [F4223, A38972]. Nevertheless, it has been determined that this main circulating metabolite has negligible affinity for 5-HT(4) receptors in vitro [F4223, A38972]. 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 [A38972].
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) [F4223].; ; 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 [F4223]. 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 [F4223].
DESCRIPTION There is some ambiguity as to the exact structure of tegaserod. The structure shown here is PubChem match using the CAS number submitted to the WHO for the INN. Alternative structure renderings for tegaserod are numerous: PubChem CID 5362436 has the highest submitter consensus in PubChem but may not match renderings in references for the biological activity; CID 5487301, and CHEMBL76370 are further alternatives.
Marketed formulations include tegaserod maleate (PubChem CID 6918369)- again with the caveat of alternative representations. (GtoPdb)
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 [A11044, A176762, F4223].; ; 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 [F4223, F4229]. No subject receiving the agent had an absolute QTcF above 480 ms [F4223, F4229]. An increase in QTcF of 30 to 60 ms was observed in 7% of patients receiving tegaserod and 8% receiving placebo [F4223, F4229]. An increase in QTcF of greater than 60 ms was observed in 0.3% and 0.2% of subjects, respectively [F4223, F4229]. The effects of tegaserod on the QTcF interval were ultimately not considered to be clinically meaningful [F4223, F4229].; ; Furthermore, it was determined that there is a potential for tegaserod and its main metabolite (the M29 metabolite) to increase platelet aggregation in vitro [F4223, F4229]. 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) [F4223, F4229]. 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 [F4223, F4229]. The clinical implications of these in vitro platelet aggregation results remain unclear [F4223, F4229].
DESCRIPTION FFA1 (GPR40) agonist; also inhibits ATP citrate lyase (Tocris Bioactive Compound Library)
DESCRIPTION 5-HT4 partial agonist (Tocriscreen Plus)
Cell lines
1
Organisms
0
Compound Sets
21
Cayman Chemical Bioactives
14692
ChEMBL Approved Drugs
CHEMBL1516474
CHEMBL76370
ChEMBL Drugs
CHEMBL1516474
CHEMBL76370
Drug Repurposing Hub
DrugBank
DB01079
DrugBank Approved Drugs
DB01079
DrugMAP
DM3XYD1
DrugMAP Approved Drugs
DM3XYD1
Guide to Pharmacology
226
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL76370
MedChem Express Bioactive Compound Library
HY-14153A
HY-14153
NCATS Inxight Approved Drugs
E5XNT3RF5A
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
tegaserod-maleate
TargetMol Bioactive Compound Library
T1551
The Spectrum Collection
Tocris Bioactive Compound Library
4613
Tocriscreen Plus
4613
Withdrawn 2.0
w60
ZINC Tool Compounds
ZINC000001545565
External IDs
53
Properties
(calculated by RDKit )
Molecular Weight
301.19
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
4
Rotatable Bonds
7
Ring Count
2
Aromatic Ring Count
2
cLogP
2.81
TPSA
85.29
Fraction CSP3
0.38
Chiral centers
0.0
Largest ring
6.0
QED
0.27
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
7-TM Receptors
Pathway
GPCR/G protein
Neuroscience
Apoptosis
Neuronal Signaling
Target
5-HT
Sert (Sodium-dependent)
HTR2A, HTR2B, HTR2C, HTR4
5-HT Receptor
Primary Target
5-HT4 Receptors
MOA
Agonist
5-HT Receptor antagonist
serotonin receptor partial agonist
ATC
A06AX06
Toxicity type
cardiovascular
Source data