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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/05/14 04:03:12」(JST)

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Tegaserod is a 5-HT₄ agonist manufactured by Novartis and sold under the names Zelnorm and Zelmac for the management of irritable bowel syndrome and constipation.^[1] Approved by the FDA in 2002, it was subsequently removed from the market in 2007 due to FDA concerns about possible adverse cardiovascular effects. Before then, it 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. Its use was also approved to treat chronic idiopathic constipation.^[2]

Mechanism of action

The drug functions as a motility stimulant, achieving its desired therapeutic effects through activation of the 5-HT₄ receptors of the enteric nervous system in the gastrointestinal tract. It also stimulates gastrointestinal motility and the peristaltic reflex, and allegedly reduces abdominal pain.^[3] Additionally, tegaserod is a 5-HT_2B receptor antagonist.^[4]

Withdrawal from market

On March 30, 2007, the U.S. Food and Drug Administration requested that Novartis withdraw Zelnorm from shelves.^[5] The FDA alleges a relationship between prescriptions of the drug and increased risks of heart attack or stroke. An analysis of data collected on over 18,000 patients demonstrated adverse cardiovascular events in 13 of 11,614 patients treated with Zelnorm (a rate of 0.11%) as compared with 1 of 7,031 patients treated with placebo (a rate of 0.01%). Novartis alleges all of the affected patients had preexisting cardiovascular disease or risk factors for such, and further alleges that no causal relationship between tegaserod use and cardiovascular events has been demonstrated.^[6] On the same day as the FDA announcement, Novartis Pharmaceuticals Canada announced that it was suspending marketing and sales of the drug in Canada in response to a request from Health Canada.^[7] Some manufacturers in India, such as Cipla and Torrent Pharmaceuticals Ltd., seem to still have generic tegaserod available in their listings^[8] and some online merchants may be selling it, despite the drug being banned in India in 2011.^[9] In a large cohort study based on a US health insurance database, no increase in the risk of cardiovascular events were found under tegaserod treatment.^[10]

Currently, tegaserod may only be used in emergency situations only with prior authorization from the FDA.^[11]

References

^ "New Data for Zelnorm". Retrieved March 30, 2007.
^ "FDA approves first treatment for women with irritable-bowel syndrome". Archived from the original on February 5, 2007. Retrieved March 30, 2007.
^ Rossi, S. (2004). Australian Medicines Handbook. Adelaide: Health Communication Network. ISBN 0-9578521-4-2.
^ Beattie DT, Smith JA, Marquess D, et al. (November 2004). "The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo". Br. J. Pharmacol. 143 (5): 549–60. doi:10.1038/sj.bjp.0705929. PMC 1575425. PMID 15466450.
^ "FDA Announces Discontinued Marketing of GI Drug, Zelnorm, for Safety Reasons". FDA Press Release. 30 March 2007.
^ "Zelnorm" (PDF). Novartis. Archived from the original on 2007-04-10. Retrieved 2007-03-30.
^ "Novartis suspends Canadian marketing and sales of Zelnorm in response to request from Health Canada". Retrieved 2007-03-30.
^ Cipla - Product List
^ "Drugs banned in India". Central Drugs Standard Control Organization, Dte.GHS, Ministry of Health and Family Welfare, Government of India. Retrieved 2013-09-17.
^ "Tegaserod and the Risk of Cardiovascular Ischemic Events: An Observational Cohort Study.". Retrieved March 3, 2010.
^ http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm103223.htm

UpToDate Contents

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1. 過敏性腸症候群の治療 treatment of irritable bowel syndrome
2. 成人における慢性便秘のマネージメント management of chronic constipation in adults
3. 悪性腫瘍関連胃不全麻痺：病態生理およびマネージメント malignancy associated gastroparesis pathophysiology and management
4. 機能性胃腸症 functional dyspepsia
5. 小腸内細菌過剰繁殖の治療 treatment of small intestinal bacterial overgrowth

English Journal

Luminal 5-HT stimulates colonic bicarbonate secretion in rats.

Kaji I1,2, Akiba Y1,2,3, Said H4, Narimatsu K1, Kaunitz JD1,5,2,3.
British journal of pharmacology.Br J Pharmacol.2015 Oct;172(19):4655-70. doi: 10.1111/bph.13216. Epub 2015 Aug 26.
BACKGROUND AND PURPOSE: The bioactive monoamine 5-HT, implicated in the pathogenesis of functional gastrointestinal disorders, is abundantly synthesized and stored in rat proximal colonic mucosa and released to the gut lumen and subepithelial space. Despite much data regarding its expression and fun
PMID 26061462

Identification and Mechanistic Investigation of Drug-Drug Interactions Associated With Myopathy: A Translational Approach.

Han X1,2,3, Quinney SK2,4,5, Wang Z2,6, Zhang P2, Duke J7, Desta Z3,5, Elmendorf JS8, Flockhart DA3,5, Li L2,3,6,7.
Clinical pharmacology and therapeutics.Clin Pharmacol Ther.2015 Sep;98(3):321-7. doi: 10.1002/cpt.150.
Myopathy is a group of muscle diseases that can be induced or exacerbated by drug-drug interactions (DDIs). We sought to identify clinically important myopathic DDIs and elucidate their underlying mechanisms. Five DDIs were found to increase the risk of myopathy based on analysis of observational da
PMID 25975815

A high-throughput method for predicting drug effects on gut transit time using larval zebrafish.

Cassar S1, Huang X2, Cole T2.
Journal of pharmacological and toxicological methods.J Pharmacol Toxicol Methods.2015 Aug 24;76:72-75. doi: 10.1016/j.vascn.2015.08.156. [Epub ahead of print]
INTRODUCTION: Zebrafish are an attractive vertebrate model due to their small size, transparency through organogenesis, and high fecundity. The zebrafish gastrointestinal (GI) tract is similar to the mammalian GI tract in gene expression, nervous system control, and response to chemical challenges.
PMID 26311656

Japanese Journal

排便と健康

浦尾正彦
順天堂醫事雑誌 60(1), 16-24, 2014
便秘とは，排便の頻度が週2回以下で，便が硬く，排便困難，残便感がある状態といわれている．実際には放置されていたり自己流の対処をされていることが多い．が，便秘患者では労働生産性が障害されたり，肛門疾患や結腸癌などの様々なリスクも増加することが知られており，しっかり取り組むべき疾患である．慢性便秘は，症候性，薬剤性，器質性，機能性便秘などに分類される．症候性便秘は神経疾患，内分泌疾患の症状の一部として …
NAID 130004684311

Contribution of Active and Inactive States of the Human 5-HT_<4d> Receptor to the Functional Activities of 5-HT_4-Receptor Agonists

Mikami Tadayoshi,Sugimoto Hiromi,Naganeo Rie [他],OHMI Takashi,SAITO Toshiyuki,EDA Hiroyuki
Journal of pharmacological sciences 107(3), 251-259, 2008-07-20
… In competitive binding assays, full agonists such as 5-methoxytryptamine and tegaserod showed 2- to 8-fold higher affinities for [3H]5-HT binding (KH) than for [3H]GR113,808 binding (KL) (KH<KL). …
NAID 10024321238

Determination of tegaserod by LC-ESI-MS/MS and its application to a pharmacokinetic study in healthy Chinese volunteers

ZOU Jian-Jun,BIAN Xiao-Jie,DING Li,ZHU Yu-Bin,FAN Hong-Wei,XIAO Da-Wei
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 861(1), 151-157, 2008-01-01
NAID 10024541695

「テガセロッド」

Tegaserod
Systematic (IUPAC) name
	(2E)-2-[(5-Methoxy-1H-indol-3-yl)methylene]-N-pentylhydrazinecarboximidamide
Clinical data
AHFS/Drugs.com	monograph
Pregnancy cat.	B3 (AU) B (US)
Legal status	Usage requires authorization from the FDA (US)
Routes	Oral
Pharmacokinetic data
Bioavailability	10%
Protein binding	98%
Metabolism	Gastric and hepatic
Half-life	11 ± 5 hours
Excretion	Fecal and renal
Identifiers
CAS number	189188-57-6
ATC code	A06AX06
PubChem	CID 5362436
DrugBank	DB01079
ChemSpider	10609889
UNII	458VC51857
KEGG	D02730
ChEMBL	CHEMBL76370
Chemical data
Formula	C16H23N5O
Mol. mass	301.39 g/mol
	SMILES CCCCCNC(=N)N\N=C\c2cnc1ccc(cc12)OC;
	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+ ; Key:IKBKZGMPCYNSLU-RGVLZGJSSA-N ;
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