WordNet

a salt or ester of maleic acid; used as a nontricyclic antidepressant drug for psychomotor activation

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/01/30 21:44:47」(JST)

wiki en

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[edit]

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[edit]

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[edit]

^ "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. Cite uses deprecated parameters (help)
^ "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

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 過敏性腸症候群の治療 treatment of irritable bowel syndrome
2. 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
3. 成人における慢性便秘のマネージメント management of chronic constipation in adults
4. 小腸内細菌過剰繁殖の治療 treatment of small intestinal bacterial overgrowth
5. 機能性胃腸症 functional dyspepsia

English Journal

An in vitro investigation of the cardiovascular effects of the 5-HT(4) receptor selective agonists, velusetrag and TD-8954.

Beattie DT, Higgins DL, Ero MP, Amagasu SM, Vickery RG, Kersey K, Hopkins A, Smith JA.SourceTheravance, Inc., 901 Gateway Boulevard, South San Francisco, CA 94080, USA. Electronic address: dbeattie@theravance.com.
Vascular pharmacology.Vascul Pharmacol.2013 Jan;58(1-2):150-6. doi: 10.1016/j.vph.2012.11.002. Epub 2012 Nov 29.
The 5-HT(4) receptor agonists, and gastrointestinal (GI) prokinetic agents, cisapride and tegaserod, lack selectivity for the 5-HT(4) receptor. Cisapride is a potent human ether-à-go-go-related gene (hERG) potassium channel inhibitor while cisapride and tegaserod have significant affinity for 5-HT(
PMID 23201772

The Zelnorm epidemiologic study (ZEST): a cohort study evaluating incidence of abdominal and pelvic surgery related to tegaserod treatment.

Seeger JD, Quinn S, Earnest DL, Lembo A, Kuo B, Rivero E, Walker AM.SourceBrigham & Women's Hospital and Harvard Medical School, Boston, MA, USA. jdseeger@partners.org.
BMC gastroenterology.BMC Gastroenterol.2012 Nov 30;12:171. doi: 10.1186/1471-230X-12-171.
ABSTRACT:BACKGROUND: Pre-marketing clinical studies of tegaserod suggested an increased risk of abdominal surgery, particularly cholecystectomy. We sought to quantify the association between tegaserod use and the occurrence of abdominal or pelvic surgery, including cholecystectomy.METHODS: This coho
PMID 23198861

Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats.

Yan C, Xin-Guang L, Hua-Hong W, Jun-Xia L, Yi-Xuan L.SourceDepartment of Gastroenterology, Peking University First Hospital, Beijing, China.
Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.].Braz J Med Biol Res.2012 Oct;45(10):948-54. Epub 2012 Jul 26.
Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT(4) receptor and the serotonin transporter (SERT
PMID 22832600

Japanese Journal

Tegaserod maleate in the treatment of irritable bowel syndrome : a clinical review

RIVKIN A.
Clin Ther 25, 1952-1974, 2003
NAID 30010442792

Related Pictures

★リンクテーブル★

リンク元	「テガセロッド」
関連記事	「maleate」

「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 ;
(what is this?) (verify)