TEGASEROD MALEATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H23N5O.C4H4O4
Molecular Weight	417.4589
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.CCCCCNC(=N)N\N=C\C1=CNC2=C1C=C(OC)C=C2

InChI

InChIKey=CPDDZSSEAVLMRY-FEQFWAPWSA-N

InChI=1S/C16H23N5O.C4H4O4/c1-3-4-5-8-18-16(17)21-20-11-12-10-19-15-7-6-13(22-2)9-14(12)15;5-3(6)1-2-4(7)8/h6-7,9-11,19H,3-5,8H2,1-2H3,(H3,17,18,21);1-2H,(H,5,6)(H,7,8)/b20-11+;2-1-

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11207504 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021200s014lbl.pdf

Tegaserod (3‐(5‐methoxy‐1H‐indol‐3ylmethylene)‐N‐pentyl‐carbazimidamide), an aminoguanidine indole derivative of serotonin, is a selective partial agonist highly selective for 5‐HT4 receptor with an affinity constant in the nanomolar range. Tegaserod, by acting as an agonist at neuronal 5-HT4 receptors, triggers the release of further neurotransmitters such as calcitonin gene-related peptide from sensory neurons. The activation of 5-HT4 receptors in the gastrointestinal tract stimulates the peristaltic reflex and intestinal secretion, as well as inhibits visceral sensitivity. In vivo studies showed that tegaserod enhanced basal motor activity and normalized impaired motility throughout the gastrointestinal tract. Zelnorm® (tegaserod maleate) is indicated for the short-term treatment of women with irritable bowel syndrome (IBS) whose primary bowel symptom is constipation. In addition Zelnorm® is indicated for the treatment of patients less than 65 years of age with chronic idiopathic constipation.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 4 (5-HT4) receptor 39 Target ID: CHEMBL1875 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021200s014lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/23756062	Partial Agonist 290		1.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Constipation 112 Sources: https://adisinsight.springer.com/drugs/800006410 https://www.ncbi.nlm.nih.gov/pubmed/18360619	Primary		Approved 8429	ZELNORM Approved Use Zelnorm® (tegaserod maleate) is indicated for the short-term treatment of women with irritable bowel syndrome (IBS) whose primary bowel symptom is constipation. The safety and effectiveness of Zelnorm in men with IBS with constipation have not been established. Zelnorm® (tegaserod maleate) is indicated for the treatment of patients less than 65 years of age with chronic idiopathic constipation. The effectiveness of Zelnorm in patients 65 years or older with chronic idiopathic constipation has not been established (see Geriatric Use). The efficacy of Zelnorm for the treatment of IBS with constipation or chronic idiopathic constipation has not been studied beyond 12 weeks. Launch Date 1.02479043E12

C_max

Value	Dose	Co-administered	Analyte	Population
2.9 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:		TEGASEROD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
10.5 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:		TEGASEROD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.35 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:		TEGASEROD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:		TEGASEROD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: FASTED

Doses

Dose	Population	Adverse events
6 mg 2 times / day steady, oral Recommended Dose: 6 mg, 2 times / day Route: oral Route: steady Dose: 6 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf Page: 4	unhealthy, <65 years n = 1184 Health Status: unhealthy Condition: IBS-C Age Group: <65 years Sex: F Population Size: 1184 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf Page: 4	Disc. AE: Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea (1.6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf Page: 4
6 mg 2 times / day steady, oral Recommended Dose: 6 mg, 2 times / day Route: oral Route: steady Dose: 6 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16678076/ Page: 609	unhealthy, adult n = 881 Health Status: unhealthy Condition: chronic constipation/ idiopathic constipation Age Group: adult Sex: unknown Population Size: 881 Sources: https://pubmed.ncbi.nlm.nih.gov/16678076/ Page: 609	Disc. AE: Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea (5.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/16678076/ Page: 609
2 mg 2 times / day steady, oral Studied dose Dose: 2 mg, 2 times / day Route: oral Route: steady Dose: 2 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16678076/ Page: 609	unhealthy, adult n = 861 Health Status: unhealthy Condition: chronic constipation/ idiopathic constipation Age Group: adult Sex: unknown Population Size: 861 Sources: https://pubmed.ncbi.nlm.nih.gov/16678076/ Page: 609	Disc. AE: Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea (3.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/16678076/ Page: 609

AEs

AE	Significance	Dose	Population
Diarrhea	1.6% Disc. AE	6 mg 2 times / day steady, oral Recommended Dose: 6 mg, 2 times / day Route: oral Route: steady Dose: 6 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf Page: 4	unhealthy, <65 years n = 1184 Health Status: unhealthy Condition: IBS-C Age Group: <65 years Sex: F Population Size: 1184 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf Page: 4
Diarrhea	5.7% Disc. AE	6 mg 2 times / day steady, oral Recommended Dose: 6 mg, 2 times / day Route: oral Route: steady Dose: 6 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16678076/ Page: 609	unhealthy, adult n = 881 Health Status: unhealthy Condition: chronic constipation/ idiopathic constipation Age Group: adult Sex: unknown Population Size: 881 Sources: https://pubmed.ncbi.nlm.nih.gov/16678076/ Page: 609
Diarrhea	3.3% Disc. AE	2 mg 2 times / day steady, oral Studied dose Dose: 2 mg, 2 times / day Route: oral Route: steady Dose: 2 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16678076/ Page: 609	unhealthy, adult n = 861 Health Status: unhealthy Condition: chronic constipation/ idiopathic constipation Age Group: adult Sex: unknown Population Size: 861 Sources: https://pubmed.ncbi.nlm.nih.gov/16678076/ Page: 609

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 inducer 781	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP1A2 1524 MATE1 306 MATE2 263 BCRP 699	BCRP 561 P-gp 1537 OAT1 326 OAT3 339 OCT1 327 OCT2 355 OATP1B1 406 OATP1B3 350 MATE1 135 MATE2 96 BSEP 52	CYP2B6 547 CYP1A2 701

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-200_Zelnorm_biopharmr_P1.pdf#page=17 Page: 17,18	inconclusive	no (co-administration study) Comment: administration with theophylline did not affect PK of theophylline Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-200_Zelnorm_biopharmr_P1.pdf#page=17 Page: 17,18
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-200_Zelnorm_biopharmr_P1.pdf#page=17 Page: 17,18	inconclusive	no (co-administration study) Comment: administration with dextromethorphan did not affect PK of dextromethorphan Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-200_Zelnorm_biopharmr_P1.pdf#page=17 Page: 17,18
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	likely
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	likely
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	likely
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	limited
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-200_Zelnorm_biopharmr_P1.pdf#page=17 Page: 17.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-200_Zelnorm_biopharmr_P1.pdf#page=17 Page: 17.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-200_Zelnorm_biopharmr_P1.pdf#page=17 Page: 17.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-200_Zelnorm_biopharmr_P1.pdf#page=17 Page: 17.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-200_Zelnorm_biopharmr_P1.pdf#page=17 Page: 17.0	no

Drug as victim

Target	Modality	Activity
BSEP 52	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	no
MATE1 135	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	no
MATE2 96	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	no
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	no
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	yes
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021200Orig1s015lbl.pdf#page=12 Page: 12.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-200_Zelnorm_pharmr_P1.pdf#page=24 Page: 24.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:51043	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:51043
ZINC	ZINC000001545565	http://zinc15.docking.org/substances/ZINC000001545565
eMolecules	902539	https://www.emolecules.com/cgi-bin/more?vid=902539

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

IBS with Constipation: The recommended dosage of Zelnorm® (tegaserod maleate) is 6 mg taken twice daily orally before meals for 4 to 6 weeks. For those women who respond to therapy at 4-6 weeks, an additional 4-6 week course can be considered. Chronic Idiopathic Constipation: The recommended dosage of Zelnorm is 6 mg taken twice daily orally before meals. Physicians and patients should periodically assess the need for continued therapy.

Route of Administration: Oral

In Vitro Use Guide

Exposure of rat colonic mucosa to tegaserod in the range of 5 nM to 5 muM for 5 or 10 min caused rapid time- and concentration-dependent desensitization of the peristaltic reflex induced by mucosal stroking. Samples of whole blood-citrate mixtures were incubated with different tegaserod concentrations mimicking human Cmax values (10 nM), 3.3 times, and 10 times Cmax for at least 1 hour.

Name

Type

Language

TEGASEROD MALEATE

Official Name

English

TEGASEROD MALEATE [MI]

Common Name

English

Tegaserod maleate [WHO-DD]

Common Name

English

3-(5-Methoxy-1H-indol-3-ylmethylene)-N-pentylcarbazimidamide hydrogen maleate

Systematic Name

English

TEGASEROD MALEATE [ORANGE BOOK]

Common Name

English

NSC-760425

Code

English

TEGASEROD MALEATE [VANDF]

Common Name

English

HYDRAZINECARBOXIMIDAMIDE, 2-((5-METHOXY-1H-INDOL-3-YL)METHYLENE)-N-PENTYL-, (2E)-, (2Z)-2-BUTENEDIOATE (1:1)

Systematic Name

English

HYDRAZINECARBOXIMIDAMIDE,2-((5-METHOXY-1H-INDOL-3-YL)METHYLENE)-N-PENTYL (2Z)-2-BUTENEDIOATE(1:1)

Common Name

English

HTF-919

Code

English

TEGASEROD MALEATE [USAN]

Common Name

English

TEGASEROD MALEATE [MART.]

Common Name

English

ZELNORM

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66885