Tegaserod

Tegaserod

Systematic (IUPAC) name
(2E)-2-[(5-Methoxy-1H-indol-3-yl)methylene]-N-pentylhydrazinecarboximidamide
Clinical data
Trade names	Zelnorm, Zelmac
AHFS/Drugs.com	monograph
Pregnancy category	AU: B3 US: B (No risk in non-human studies)
Legal status	US: Usage requires authorization from the FDA
Routes of administration	Oral
Pharmacokinetic data
Bioavailability	10%
Protein binding	98%
Metabolism	Gastric and hepatic
Biological half-life	11 ± 5 hours
Excretion	Fecal and renal
Identifiers
CAS Number	189188-57-6 N
ATC code	A06AX06 (WHO)
PubChem	CID: 5362436
IUPHAR/BPS	226
DrugBank	DB01079 Y
ChemSpider	10609889 Y
UNII	458VC51857 Y
KEGG	D02730 Y
ChEMBL	CHEMBL76370 Y
Chemical data
Formula	C16H23N5O
Molecular 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+ Y Key:IKBKZGMPCYNSLU-RGVLZGJSSA-N Y
NY (what is this?)  (verify)

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. 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.

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. Additionally, tegaserod is a 5-HT_2B receptor antagonist.

Withdrawal from market

On 30 March 2007, the United States 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. 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. 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. 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. Currently, tegaserod may only be used in emergency situations only with prior authorization from the FDA.