Benfluorex

Benfluorex

Systematic (IUPAC) name
(RS)-2-({1-[3-(trifluoromethyl)phenyl]propan- 2-yl}amino)ethyl benzoate
Clinical data
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral
Pharmacokinetic data
Excretion	Renal
Identifiers
CAS Number	23602-78-0 Y
ATC code	A10BX06 (WHO)
PubChem	CID: 2318
DrugBank	DB09022 N
ChemSpider	2228 Y
UNII	403FO0NQG3 Y
KEGG	D07192 Y
ChEMBL	CHEMBL400599 Y
Chemical data
Formula	C19H20F3NO2
Molecular mass	351.363 g/mol
SMILES FC(F)(F)c1cccc(c1)CC(NCCOC(=O)c2ccccc2)C
InChI InChI=1S/C19H20F3NO2/c1-14(12-15-6-5-9-17(13-15)19(20,21)22)23-10-11-25-18(24)16-7-3-2-4-8-16/h2-9,13-14,23H,10-12H2,1H3 Y Key:CJAVTWRYCDNHSM-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Benfluorex is an anorectic and hypolipidemic agent that is structurally related to fenfluramine patented and manufactured by a French pharmaceutical company Servier. Two clinical studies have shown it may improve glycemic control and decrease insulin resistance in people with poorly controlled type 2 diabetes. However, Servier is suspected of having marketed Mediator (benfluorex) at odds with the drug's medical properties.

Drug withdrawn

On 18 December 2009, the European Medicines Agency (EMA) recommended the withdrawal of all medicines containing benfluorex in the European Union, because their risks, particularly the risk of heart valve disease (fenfluramine-like cardiovascular side-effects), are greater than their benefits. Thus Frachon et al. showed a significantly higher prevalence of unexplained valvular heart disease in patients taking benfluorex compared to controls. and Weill et al. looked at over 1 million diabetic patients demonstrating a higher hospitalization rate in benfluorex takers for valvular heart disease.

In France the medication had been marketed as by Servier as an adjuvant antidiabetic under the name Mediator. The drug was on the market between 1976 and 2009 and is thought to have caused between 500 – 2,000 deaths. The drug was also used in Spain (trade name, Modulator), Portugal and Cyprus.

Fenfluramine, a related drug, had been withdrawn from the market in 1997 after reports of heart valve disease, pulmonary hypertension, and development of cardiac fibrosis. This side effect is mediated by the metabolite norfenfluramine on 5HT_2B receptors of heart valves (Rothman et al., Circulation 2000), leading to a characteristic pattern of heart failure following proliferation of cardiac fibroblasts on the tricuspid valve. Both fenfluramine and benfluorex form norfenfluramine as a metabolite. This side effect led to the withdrawal of fenfluramine as an anorectic drug worldwide, and later to the withdrawal of benfluorex in Europe.

References

• Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL.(2000). "Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications." Circulation 102(23):2836-41. PMID 11104741