Tegaserod - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Spectra Taxonomy

Targets (4)Enzymes (5)Transporters (1)

Targets (4)Enzymes (5)Transporters (1)Biointeractions (13)

Identification

Name

Tegaserod

Accession Number

DB01079 (APRD00096)

Type

Small Molecule

Groups

Investigational, Withdrawn

Description

Tegaserod is a 5-HT4 agonist manufactured by Novartis and used for the management of irritable bowel syndrome and constipation. Its use was the only drug approved by the United States Food and Drug Administration to help relieve the abdominal discomfort, bloating and constipation associated with irritable bowel syndrome. On March 30, 2007, the U.S. Food and Drug Administration requested that Novartis withdraw Zelnorm from shelves. The FDA alleges a relationship between prescriptions of the drug and increased risks of heart attack or stroke. [Wikipedia]

Structure

MOL SDF PDB SMILES InChI

Synonyms

1-(((5-Methoxyindol-3-yl)methylene)amino)-3-pentylguanidine

tégasérod

tegaserodum

External IDs

SDZ HTF 919

Product Ingredients

Ingredient	UNII	CAS	InChI Key	Details
Tegaserod maleate	E5XNT3RF5A	189188-57-6	CPDDZSSEAVLMRY-FEQFWAPWSA-N	Details

Approved Prescription Products

Not Available

Approved Generic Prescription Products

Not Available

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Name	Company
Zelmac	Not Available
Zelnorm	Not Available

Brand mixtures

Not Available

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

Provides relief from the symptoms of irritable bowel syndrome including chronic idiopathic constipation.

Structured Indications

Not Available

Pharmacodynamics

Tegaserod is indicated for the short-term treatment of women with irritable bowel syndrome (IBS) whose primary bowel symptom is constipation. Irritable bowel syndrome with constipation and chronic idiopathic constipation are both lower gastrointestinal dysmotility disorders. Clinical investigations have shown that both motor and sensory functions of the gut appear to be altered in patients suffering from irritable bowel syndrome (IBS), while in patients with chronic idiopathic constipation, reduced intestinal motility is the predominant cause of the condition. Both the enteric nervous system, which acts to integrate and process information in the gut, and 5-hydroxytryptamine (5-HT, serotonin) are thought to represent key elements in the etiology of both IBS and idiopathic constipation. Approximately 95% of serotonin is found throughout the gastrointestinal tract, primarily stored in enterochromaffin cells but also in enteric nerves acting as a neurotransmitter. Serotonin has been shown to be involved in regulating motility, visceral sensitivity and intestinal secretion. Investigations suggest an important role of serotonin Type-4 (5-HT₄) receptors in the maintenance of gastrointestinal functions in humans. 5-HT₄ receptor mRNA has been found throughout the human gastrointestinal tract.

Mechanism of action

Tegaserod is a 5-HT₄ receptor partial agonist that binds with high affinity at human 5-HT₄ receptors, whereas it has no appreciable affinity for 5-HT₃ or dopamine receptors. It has moderate affinity for 5-HT₁ receptors. 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.

Target	Kind	Pharmacological action	Actions	Organism	UniProt ID
5-hydroxytryptamine receptor 4	Protein	yes	antagonist partial agonist	Human	Q13639	details
5-hydroxytryptamine receptor 2B	Protein	unknown	antagonist	Human	P41595	details
5-hydroxytryptamine receptor 2C	Protein	unknown	antagonist	Human	P28335	details
5-hydroxytryptamine receptor 2A	Protein	unknown	antagonist	Human	P28223	details

Absorption

Rapidly absorbed after oral administration, with an absolute bioavailability of approximately 10%.

Volume of distribution

368 ± 223 L

Protein binding

98%

Metabolism

Tegaserod is metabolized mainly via two pathways. The first is a presystemic acid catalyzed hydrolysis in the stomach followed by oxidation and conjugation which produces the main metabolite of tegaserod, 5-methoxyindole-3-carboxylic acid glucuronide. The main metabolite has negligible affinity for 5-HT₄ receptors in vitro. The second metabolic pathway of tegaserod is direct glucuronidation which leads to generation of three isomeric N-glucuronides.

Route of elimination

Approximately two-thirds of the orally administered dose of tegaserod is excreted unchanged in the feces, with the remaining one-third excreted in the urine, primarily as the main metabolite.

Half life

11 ± 5 hours

Clearance

77 +/- 15 L/h [IV administration]

Toxicity

Oral LD₅₀ in rat is 2000 mg/kg.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction	Drug group
Abiraterone	The serum concentration of Tegaserod can be increased when it is combined with Abiraterone.	Approved
Amiodarone	The metabolism of Tegaserod can be decreased when combined with Amiodarone.	Approved, Investigational
Amodiaquine	The serum concentration of Amodiaquine can be increased when it is combined with Tegaserod.	Approved
Artemether	The metabolism of Tegaserod can be decreased when combined with Artemether.	Approved
Atomoxetine	The metabolism of Tegaserod can be decreased when combined with Atomoxetine.	Approved
Betaxolol	The metabolism of Tegaserod can be decreased when combined with Betaxolol.	Approved
Bupropion	The metabolism of Tegaserod can be decreased when combined with Bupropion.	Approved
Celecoxib	The metabolism of Tegaserod can be decreased when combined with Celecoxib.	Approved, Investigational
Chloroquine	The metabolism of Tegaserod can be decreased when combined with Chloroquine.	Approved, Vet Approved
Chlorpromazine	The metabolism of Tegaserod can be decreased when combined with Chlorpromazine.	Approved, Vet Approved
Cholecalciferol	The metabolism of Tegaserod can be decreased when combined with Cholecalciferol.	Approved, Nutraceutical
Cimetidine	The metabolism of Tegaserod can be decreased when combined with Cimetidine.	Approved
Cinacalcet	The metabolism of Tegaserod can be decreased when combined with Cinacalcet.	Approved
Citalopram	The metabolism of Tegaserod can be decreased when combined with Citalopram.	Approved
Clemastine	The metabolism of Tegaserod can be decreased when combined with Clemastine.	Approved
Clobazam	The metabolism of Tegaserod can be decreased when combined with Clobazam.	Approved, Illicit
Clomipramine	The metabolism of Tegaserod can be decreased when combined with Clomipramine.	Approved, Vet Approved
Clotrimazole	The metabolism of Tegaserod can be decreased when combined with Clotrimazole.	Approved, Vet Approved
Clozapine	The metabolism of Tegaserod can be decreased when combined with Clozapine.	Approved
Cobicistat	The serum concentration of Tegaserod can be increased when it is combined with Cobicistat.	Approved
Cocaine	The metabolism of Tegaserod can be decreased when combined with Cocaine.	Approved, Illicit
Darifenacin	The metabolism of Tegaserod can be decreased when combined with Darifenacin.	Approved, Investigational
Darunavir	The serum concentration of Tegaserod can be increased when it is combined with Darunavir.	Approved
Delavirdine	The metabolism of Tegaserod can be decreased when combined with Delavirdine.	Approved
Desipramine	The metabolism of Tegaserod can be decreased when combined with Desipramine.	Approved
Diphenhydramine	The metabolism of Tegaserod can be decreased when combined with Diphenhydramine.	Approved
Dronedarone	The metabolism of Tegaserod can be decreased when combined with Dronedarone.	Approved
Duloxetine	The metabolism of Tegaserod can be decreased when combined with Duloxetine.	Approved
Eliglustat	The metabolism of Tegaserod can be decreased when combined with Eliglustat.	Approved
Fesoterodine	The serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Tegaserod.	Approved
Fluoxetine	The metabolism of Tegaserod can be decreased when combined with Fluoxetine.	Approved, Vet Approved
Fluvoxamine	The metabolism of Tegaserod can be decreased when combined with Fluvoxamine.	Approved, Investigational
Haloperidol	The metabolism of Tegaserod can be decreased when combined with Haloperidol.	Approved
Imipramine	The metabolism of Tegaserod can be decreased when combined with Imipramine.	Approved
Indinavir	The metabolism of Tegaserod can be decreased when combined with Indinavir.	Approved
Isoniazid	The metabolism of Tegaserod can be decreased when combined with Isoniazid.	Approved
Ketoconazole	The metabolism of Tegaserod can be decreased when combined with Ketoconazole.	Approved, Investigational
Lopinavir	The metabolism of Tegaserod can be decreased when combined with Lopinavir.	Approved
Lorcaserin	The metabolism of Tegaserod can be decreased when combined with Lorcaserin.	Approved
Lumefantrine	The metabolism of Tegaserod can be decreased when combined with Lumefantrine.	Approved
Methadone	The metabolism of Tegaserod can be decreased when combined with Methadone.	Approved
Methotrimeprazine	The metabolism of Tegaserod can be decreased when combined with Methotrimeprazine.	Approved
Metoprolol	The serum concentration of Metoprolol can be increased when it is combined with Tegaserod.	Approved, Investigational
Mirabegron	The metabolism of Tegaserod can be decreased when combined with Mirabegron.	Approved
Nevirapine	The metabolism of Tegaserod can be decreased when combined with Nevirapine.	Approved
Nicardipine	The metabolism of Tegaserod can be decreased when combined with Nicardipine.	Approved
Nilotinib	The metabolism of Tegaserod can be decreased when combined with Nilotinib.	Approved, Investigational
Panobinostat	The serum concentration of Tegaserod can be increased when it is combined with Panobinostat.	Approved, Investigational
Paroxetine	The metabolism of Tegaserod can be decreased when combined with Paroxetine.	Approved, Investigational
Peginterferon alfa-2b	The serum concentration of Tegaserod can be decreased when it is combined with Peginterferon alfa-2b.	Approved
Promazine	The metabolism of Tegaserod can be decreased when combined with Promazine.	Approved, Vet Approved
Quinidine	The metabolism of Tegaserod can be decreased when combined with Quinidine.	Approved
Quinine	The metabolism of Tegaserod can be decreased when combined with Quinine.	Approved
Ranolazine	The metabolism of Tegaserod can be decreased when combined with Ranolazine.	Approved, Investigational
Ritonavir	The metabolism of Tegaserod can be decreased when combined with Ritonavir.	Approved, Investigational
Rolapitant	The metabolism of Tegaserod can be decreased when combined with Rolapitant.	Approved
Ropinirole	The metabolism of Tegaserod can be decreased when combined with Ropinirole.	Approved, Investigational
Sertraline	The metabolism of Tegaserod can be decreased when combined with Sertraline.	Approved
Stiripentol	The metabolism of Tegaserod can be decreased when combined with Stiripentol.	Approved
Terbinafine	The metabolism of Tegaserod can be decreased when combined with Terbinafine.	Approved, Investigational, Vet Approved
Thioridazine	The serum concentration of Thioridazine can be increased when it is combined with Tegaserod.	Withdrawn
Ticlopidine	The metabolism of Tegaserod can be decreased when combined with Ticlopidine.	Approved
Tipranavir	The metabolism of Tegaserod can be decreased when combined with Tipranavir.	Approved, Investigational
Tranylcypromine	The metabolism of Tegaserod can be decreased when combined with Tranylcypromine.	Approved
Venlafaxine	The metabolism of Tegaserod can be decreased when combined with Venlafaxine.	Approved
Ziprasidone	The metabolism of Tegaserod can be decreased when combined with Ziprasidone.	Approved

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

Not Available

External Links

Resource	Link
KEGG Drug	D06056
ChemSpider	10609889
BindingDB	79022
ChEBI	51043
ChEMBL	CHEMBL76370
Therapeutic Targets Database	DAP001526
PharmGKB	PA130413154
RxList	http://www.rxlist.com/cgi/generic3/zelnorm.htm
Drugs.com	http://www.drugs.com/cdi/tegaserod.html
Wikipedia	Tegaserod

ATC Codes

A06AX06 — Tegaserod

AHFS Codes

92:00.00

PDB Entries

Not Available

FDA label

Download (634 KB)

MSDS

Download (58.1 KB)

Clinical Trials

Phase	Status	Purpose	Conditions	Count
2	Completed	Treatment	Symptomatic Gastroespohageal Reflux Disease	1
2	Terminated	Not Available	Diabetic Gastropathy	1
2, 3	Terminated	Treatment	Occasional Constipation	1
3	Completed	Treatment	Chronic Constipation	1
3	Completed	Treatment	Gastroesophageal Reflux Disease (GERD)	2
3	Completed	Treatment	Heartburn / Indigestion	1
3	Completed	Treatment	Indigestion	5
3	Completed	Treatment	Occasional Constipation	1
3	Terminated	Treatment	Constipation Predominant / Irritable Bowel Syndrome (IBS-C)	1
3	Terminated	Treatment	Opioid Induced Constipation (OIC)	2
4	Completed	Treatment	Chronic Constipation	1
4	Completed	Treatment	IBS-C and IBS With Mixed Bowel Habits	1
4	Completed	Treatment	Occasional Constipation	1
4	Terminated	Treatment	Chronic Constipation	1
4	Terminated	Treatment	Diabetes / Gastroparesis	1
4	Withdrawn	Treatment	Constipation and Dyspepsia	1
Not Available	No Longer Available	Not Available	Chronic Idiopathic Constipation / Constipation Predominant Irritable Bowel Syndrome	1
Not Available	Terminated	Treatment	Chronic Diseases / Occasional Constipation	1
Not Available	Unknown Status	Treatment	Occasional Constipation	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Dosage forms

Not Available

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US5510353	No	1993-04-26	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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum Type	Description	Splash Key
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	Not 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 / Imines / Hydrocarbon derivatives

Substituents

Indole / Anisole / Phenol ether / Alkyl aryl ether / Substituted pyrrole / Benzenoid / Pyrrole / Heteroaromatic compound / Guanidine / Carboximidamide

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

guanidines, indoles, carboxamidine, hydrazines (CHEBI:51043 )

Targets

Details

1. 5-hydroxytryptamine receptor 4

Kind: Protein
Organism: Human
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 is mediated by G proteins that stimulate adenylate cyclase.
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. [PubMed:11207504 ]
Kamm MA: Review article: the complexity of drug development for irritable bowel syndrome. Aliment Pharmacol Ther. 2002 Mar;16(3):343-51. [PubMed:11876686 ]
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 ]
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 ]
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 ]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Details

2. 5-hydroxytryptamine receptor 2B

Kind: Protein
Organism: Human
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 change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins ...
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. [PubMed:15466450 ]
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 ]
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 ]

Details

3. 5-hydroxytryptamine receptor 2C

Kind: Protein
Organism: Human
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-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modul...
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. [PubMed:15466450 ]

Details

4. 5-hydroxytryptamine receptor 2A

Kind: Protein
Organism: Human
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-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates...
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. [PubMed:15466450 ]

Enzymes

Details

1. Cytochrome P450 1A2

Kind: Protein
Organism: Human
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:: CYP1A2
Uniprot ID:: P05177
Uniprot Name:: Cytochrome P450 1A2
Molecular Weight:: 58293.76 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Details

2. Cytochrome P450 2C8

Kind: Protein
Organism: Human
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:: CYP2C8
Uniprot ID:: P10632
Uniprot Name:: Cytochrome P450 2C8
Molecular Weight:: 55824.275 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Details

3. Cytochrome P450 2C9

Kind: Protein
Organism: Human
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:: CYP2C9
Uniprot ID:: P11712
Uniprot Name:: Cytochrome P450 2C9
Molecular Weight:: 55627.365 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Details

4. Cytochrome P450 2D6

Kind: Protein
Organism: Human
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 antidepressants.
Gene Name:: CYP2D6
Uniprot ID:: P10635
Uniprot Name:: Cytochrome P450 2D6
Molecular Weight:: 55768.94 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Details

5. Cytochrome P450 2E1

Kind: Protein
Organism: Human
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 or carcinogenic forms.
Gene Name:: CYP2E1
Uniprot ID:: P05181
Uniprot Name:: Cytochrome P450 2E1
Molecular Weight:: 56848.42 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Details

1. Sodium-dependent serotonin transporter

Kind: Protein
Organism: Human
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 the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin an...
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. [PubMed:17510552 ]

Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:56

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Structure for DB01079 (Tegaserod)

Targets

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Enzymes

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Transporters

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