106650-56-0 Weight Loss Powder Sibutramine Hydrochloride Monohydrate ISO9001

Pharmaceutical Grade Sibutramine Raw Powder For Loss Weight Medicine Cas 106650-56-0

Product Information

Synonym:1-[1-(4-Chlorophenyl)cyclobutyl]-N,N,3-trimethyl-butan-1-amine
CAS Number:106650-56-0
Molecular Formula:C17H26ClN
Molecular Weight:279.85
Beilstein:7623626
MDL Number:MFCD00866415
Melting Point:191-192 ??
Appearance:crystalline,powder,white

Function:

This product is to transform lipid into energy to loss weight. It can be used in the treatment of obesity, weight loss, and the maintenance of weight. The treatment should combine with low-calorie diet and physical exercise.

Pharmacodynamics

Sibutramine is a monoamine reuptake inhibitor (MRI) that, in humans, reduces the reuptake of norepinephrine (by ~73%), serotonin (by ~54%), and dopamine (by ~16%), thereby increasing the levels of these substances in synaptic clefts and helping enhance satiety; the serotonergic action, in particular, is thought to influence appetite. Older anorectic agents such as amphetamine and fenfluramine force the release of these neurotransmitters rather than affecting their reuptake.

Despite having a mechanism of action similar to tricyclic antidepressants, sibutramine has failed to demonstrate antidepressant properties in animal studies. It was approved by the U.S. Food and Drug Administration (FDA) in November 1997 for the treatment of obesity.

Sibutramine is reported to be a prodrug to two active metabolites, desmethylsibutramine (M1; BTS-54354) and didesmethylsibutramine (M2; BTS-54505), with much greater potency as MRIs.

Unlike other serotonergic appetite suppressants like fenfluramine, sibutramine and its metabolites have only low and likely inconsequential affinity for the 5-HT_2B receptor.

Chemistry

Sibutramine has usually been used in the form of the hydrochloride monohydrate salt.

Detection in body fluids

Sibutramine and its two active N-demethylated metabolites may be measured in biofluids by liquid chromatography-mass spectrometry. Plasma levels of these three species are usually in the 1–10 μg/L range in persons undergoing therapy with the drug. The parent compound and norsibutramine are often not detectable in urine, but dinorsibutramine is generally present at concentrations of >200 μg/L.

Society and culture

Regulatory approval

Studies are ongoing into reports of sudden death, heart failure, renal failure and gastrointestinal problems. Despite a 2002 petition by Ralph Nader-founded NGO Public Citizen, the FDA made no attempts to withdraw the drug, but was part of a Senate hearing in 2005.^[30] Similarly, David Graham, FDA "whistleblower", testified before a Senate Finance Committee hearing that sibutramine may be more dangerous than the conditions it is used for.

Between January 2003 and November 2005, a large randomized-controlled "Sibutramine Cardiovascular OUTcomes" (SCOUT) study with 10,742 patients examined whether or not sibutramine administered within a weight management program reduces the risk for cardiovascular complications in people at high risk for heart disease and concluded that use of silbutramine had a RR 1.16 for the primary outcome (composit of nonfatal MI, nonfatal CVA, cardiac arrest, and CV death).

In a dissenting article, "Sibutramine: gone, but not forgotten", David Haslam (chairman of the National Obesity Forum) says that the SCOUT study is flawed as it only covered high-risk patients and did not consider obese patients who do not have cardiovascular complications or similar contraindications

On January 21, 2010, the European Medicines Agency recommended suspension of marketing authorizations for sibutramine based on the SCOUT study results.

In August 2010 the FDA added a new contraindication for patients over 65 years of age due to the fact that clinical studies of sibutramine did not include sufficient numbers of such patients.

Abbott Laboratories announced on October 8, 2010 that it is withdrawing sibutramine from the US market under pressure from the FDA, citing concerns over minimal efficacy coupled with increased risk of adverse cardiovascular events.

Counterfeit weight-loss products

On December 22, 2008, the United States Food and Drug Administration issued an alert to consumers naming 27 different products marketed as “dietary supplements” for weight loss, that illegally contain undisclosed amounts of sibutramine. In March 2009, Dieter Müller et al. published a study of sibutramine poisoning cases from similar Chinese "herbal supplements" sold in Europe, containing as much as twice the dosage of the legally licensed drug.

An additional 34 products were recalled by the FDA on April 22, 2009, further underscoring the risks associated with unregulated "herbal supplements" to unsuspecting persons. This concern is especially relevant to those with underlying medical conditions incompatible with undeclared pharmaceutical adulterants. In January 2010, a similar alert was issued for counterfeit versions of the over-the-counter weight loss drug Alli sold over the Internet. Instead of the active ingredient orlistat, the counterfeit drugs contain sibutramine, and at concentrations at least twice the amount recommended for weight loss.

In March 2010 Health Canada advised the public that illegal "Herbal Diet Natural" had been found on the market, containing sibutramine, which is a prescription drug in Canada, without listing sibutramine as an ingredient. In October 2010 FDA notified consumers that "Slimming Beauty Bitter Orange Slimming Capsules contain the active pharmaceutical ingredient sibutramine, a prescription-only drug which is a stimulant. Sibutramine is not listed on the product label."

In October 2010 the MHRA in the UK issued a warning regarding "Payouji tea" and "Pai You Guo Slim Capsules" which were found to contain undeclared quantities of sibutramine.

On December 30, 2010 the FDA released a warning regarding "Fruta Planta" dietary products, which were found to contain undeclared amounts of sibutramine. The recall stated that "there is NO SAFE formula on the US market and that all versions of Fruta Planta contain sibutramine. All versions of the formula are UNSAFE and should not be purchased from any source."

Some illegal weight loss products imported into Ireland have been found to contain sibutramine. Similar concerns have been raised in Australia, where illegal imported supplements have been found to contain sibutramine, resulting in public alerts from Australia's Therapeutic Goods Administration.

In October 2011, the FDA warned that 20 brands of dietary supplements were tainted with sibutramine. In a 2018 study FDA has found synthetic additives including sibutramine in over 700 diet supplements marketed as "natural", "traditional" or "herbal remedies".