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View Full Version : Rimonabant weight loss drug profile & studies.



guardianactual
05-29-2014, 04:25 PM
This drug popped up in my email as a company (Which will not be named) is having a sale on it & I was curious to see wtf it was. NO PMs on soucing please!
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</br> Systematic (IUPAC) name 5-(4-Chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide
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</br> Halflife
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</br> 6 to 9 days with normal BMI 16 days if BMI >30
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</br> Rimonabant (also known as SR141716; trade name Acomplia) is an anorectic antiobesity drug that has been withdrawn from the market due to potentially serious side effects. It was approved for use in Europe and other countries, but never approved in the United States. Rimonabant is an inverse agonist for the cannabinoid receptor CB1.[3] Its main effect is reduction in appetite.
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</br> Uses/potential uses
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</br> Obesity In a 2006 (2 year) study reported in JAMA, "Compared with the placebo group, the 20 mg of rimonabant group produced greater mean (SEM) reductions in weight (-6.3 [0.2] kg vs -1.6 [0.2] kg; P<.001), waist circumference (-6.1 [0.2] cm vs -2.5 [0.3] cm; P<.001), and level of triglycerides (percentage change, -5.3 [1.2] vs 7.9 [2.0]; P<.001) and a greater increase in level of high-density lipoprotein cholesterol (percentage change, 12.6 [0.5] vs 5.4 [0.7]; P<.001)." [10]
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</br> Smoking cessation Rimonabant may also be found to be effective in assisting some smokers to quit smoking. Sanofi is currently conducting studies to determine the possible value of rimonabant in smoking-cessation therapy. The Studies with Rimonabant and Tobacco Use (STRATUS) program involves more than 6,000 subjects. STRATUS is designed to explore two smoking-related therapies: first, to use rimonabant directly to aid in smoking cessation; second, to help prevent weight gain in former smokers. Initial results apparently suggest rimonabant is effective for both uses. However, the FDA has explicitly stated to Sanofi that, without additional studies, rimonabant cannot be approved in the United States for smoking cessation therapy. According to a Cochrane Collaboration review in 2007, rimonabant "may increase the odds of quitting approximately 11/2-fold".[11]
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</br> Addiction behaviors Rimonabant reduced resumption of cocaine-seeking responses triggered by two of the three most common triggers of relapse in humans: priming and cues. It may also reduce ethanol- and opiate-seeking behavior.[12]
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</br> Short-term memory Tetrahydrocannabinol (THC) is known to impair short-term memory. It was therefore hypothesised that rimonabant may reduce or inhibit the atrophic effects of cannabinoids. Indeed, in animal studies, it significantly improved the ability of rats to encode information into short-term memory.[13]
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</br> Blockage of cannabis effects Rimonabant blocks the psychoactive and some of the cardiovascular effects of Δ9-tetrahydrocannabinol (THC) in humans without affecting the pharmacokinetics.[14] Rimonabant has been described colloquially as "reverse marijuana", having a depressing effect on appetite inverse to the increased appetite created by cannabinoids.[15]
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</br> Other effects Rimonabant reduces voluntary wheel running in laboratory mice.[16] Rimonabant significantly increased human sperm motility and viability in vitro.[17]
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</br> Negative side effects Shortly after market introduction, press reports and independent studies suggested that side effects occurred more intensely and more commonly than had been found by the manufacturer in their clinical studies. Reports of severe depression and suicidal thoughts were frequent.[18] As the drug's target CB1 receptors are fairly ubiquitous throughout the central nervous system, it is not currently understood where the inverse agonist is acting to cause these side-effects.
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</br> In 2007, it was reported that the committee advising the U.S. FDA had voted not to recommend the drug's approval because of concerns over suicidality, depression, and other related side effects associated with use of the drug.[19]
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</br> CHICAGO – New data demonstrate the efficacy of rimonabant in improving the atherogenic dyslipidemia profile in patients with type 2 diabetes, in addition to reducing weight and improving glycemic control.
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</br> Julio Rosenstock, MD, presented the secondary endpoint results on lipid profile from the Study Evaluating Rimonabant Efficacy in Drug-Naive Diabetic Patients (SERENADE) at the American Diabetes Association 67th Annual Scientific Sessions.
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</br> Rimonabant (Acomplia, Sanofi-Aventis) is the first drug to employ selective blockade of the cannabinoid receptor type 1 and is meant for the treatment of obesity. At a recent FDA Endocrinologic and Metabolic Drugs Advisory Committee meeting, the panel voted unanimously against recommendation of FDA approval of the drug based on psychiatric and neurologic adverse effects. Sanofi-Aventis recently withdrew the new drug application for rimonabant in June.
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</br> "Rimonabant may have a role in the overall management of type 2 diabetes in achieving meaningful reductions in HbA1c plus weight loss and improving lipid and adiponectin levels,” Rosenstock, Director of Dallas Diabetes and Endocrine Center at Medical City and clinical professor of medicine, University of Texas Southwestern Medical School, Dallas, said during the oral presentation.
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</br> SERENADE trial SERENADE was a randomized, double blind and placebo-controlled trial. It was designed to assess the effects of rimonabant 20 mg daily compared with placebo in patients with type 2 diabetes (n=278). The study was conducted for a period of six months.
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</br> The primary outcome was change in HbA1c level. Early data demonstrated a greater reduction of HbA1c from baseline in patients randomly assigned rimonabant compared with placebo and dietary intervention (0.8% vs. 0.3%; P=.0002). Patients randomly assigned rimonabant also had greater reductions in body weight (6.7 kg vs. 2.8 kg; P<.0001).
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</br> However, Rosenstock and colleagues extended the initial analyses of SERENADE and evaluated a secondary outcome of the effects of rimonabant 20 mg on atherogenic dyslipidemia, including changes in non-HDL cholesterol, LDL particle size, adiponectin and the apolipoprotein B–apolipoprotein A-I ratio in the same study population.
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</br> They discovered greater increases in HDL in patients randomly assigned rimonabant (10.1% vs. 3.2%; P<.0001). Although changes in LDL were similar between the two treatment groups, LDL particle size was increased in the rimonabant group, which resulted in a reduction of small, dense LDL (0.6% vs. 0%). Patients randomly assigned rimonabant had greater reductions in ApoB/Apo A-I (0.03 vs. 0.002; P=.0045) and increased mean adiponectin levels (1.6 vs. 0.2; P=.0001).
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</br> The drug was generally well tolerated in SERENADE, according to Rosenstock.
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</br> However, patients randomly assigned rimonabant had a greater proportion of adverse events (70% vs. 57%), including dizziness (10.9% vs. 2.1%) and nausea (8.7% vs. 3.6%).
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</br> Psychiatric events were also more common in the patients who received rimonabant, specifically depressed mood (6% vs. 1%) and anxiety (6% vs. 4%).
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</br> “Further studies are warranted to explore combinations of rimonabant with other antidiabetic agents so that the risk–benefit profile of cannabinoid receptor 1 blockers on glycemic control plus weight loss in type 2 diabetes can be fully assessed,” Rosenstock said. The benefits of rimonabant on lipid profile, weight loss and glycemic control are currently being tested in the long-term, ongoing CRESCENDO trial. – by Katie Kalvaitis