Rimonabant / SR141716A (trade name Acomplia)
N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide.
Rimonabant is a selective CB1 endocannabinoid receptor antagonist indicated for the treatment of obesity. The “CB” in CB1 stands for cannabinoid receptor type-1. The drug works primarily as an appetite suppressant and helps to control HDL (good cholesterol) levels. It works by blocking endogenous cannabinoid binding to neuronal CB1 receptors.
CB1 blockers act on the endocannabinoid system (the EC system), a natural system that modulates the body's energy balance and nicotine dependence. An over-stimulated EC system is thought to play a role in obesity and in tobacco dependence, and CB1 blockers are supposed to reduce this overstimulation.
Activation of these receptors by endoegenous cannabinoids, such as anadamide (a recently discovered messenger molecule that plays a role in pain, depression, appetite, memory, and fertility), increases appetite. As mentioned above the CB receptors are believed to play a role in controlling food consumption and dependence / habituation. People often refer to the cannabis-induced "munchies" or hunger pangs. Rimonabant attempts to do the opposite.
Patients in Despres' study saw their levels of HDL cholesterol, the good kind, rise 23% on average, while triglycerides, a kind of cholesterol that is beneficial at lower levels, fell 15%. Rimonabant appears to alter the level of cannabonoid 1 in fat cells, which could be one way that it affects cholesterol concentration.(5)
It is the only endocannabinoid receptor antagonist in clinical development and thus offers a unique therapeutic approach to appetite control and weight reduction. The drug also has potential as a treatment for smoking cessation because the endocannabinoid system is also involved in the body's response to tobacco dependence. (1)
As stated ealier Rimonabant is an experimental wonder drug, Rimonabant, helps you lose weight, quit smoking and it also helps protect your heart. Trials have shown that 33% of people on Rimonabant lost 10% of body weight and kept their weight down for two years this is a record, no other diet drug has managed to keep a person's weight down for so long.
As well as keeping you lean, the drug also helps you quit the smoking habit. This will be of great interest for many smokers who are afraid to give up because they say they will put on loads of weight if they do (young female smokers worry about this the most). (2)
Two-year data from the phase III multicentre Rimonabant In Obesity (RIO) trials, which compared rimonabant at doses of 5mg and 20mg with placebo with respect to weight reduction and prevention of weight gain, showed that the positive results seen after a year's treatment were sustained over the full two-year trial period. Consistent with the one-year data, the results showed that overweight and obese patients taking rimonabant 20mg/d achieved significant reductions in body weight, waist circumference (an indicator of abdominal obesity) and improved lipid and glycaemic profiles compared with placebo recipients. Rimonabant also had a significant impact on metabolic CVD (cardiovascular disease) risk factors, greater than that expected by weight loss alone.
Data from the RIO trials suggest rimonabant is effective for maintaining weight loss for periods of at least two years. (1)
In another study done with 1036 patients who were either overweight or obese and who had blood lipid disorders were also randomized to one of three groups (placebo vs. 5 mg/day or 20 mg/day rimonabant). After 1 year of treatment, patients receiving 20 mg rimonabant lost an average of about 20 pounds of weight, compared to 5 pounds for patients on placebo. Further, patients receiving 20 mg rimonabant had significant improvements (compared to placebo) in waist circumference, HDL levels, triglyceride levels, CRP levels, and insulin sensitivity. For patients with metabolic syndrome at baseline (which included about 50% of the study population), half of those taking 20 mg rimonabant no longer had metabolic syndrome at the end of the study. (3)
Data from another study with rimonabant evaluated the drug's effect on smoking cessation. In this study, 787 smokers (average of 23 cigarettes per day) were randomized to receive either placebo, or rimonabant in doses of either 5mg or 20mg/ed. The patients received the study drugs for 10 weeks. They were permitted to continue smoking for the first 2 weeks, but were instructed to attempt to quit smoking on Day 15. The number of patients who had not smoked during the last 4 weeks of the 10 week period were tabulated. Of patients who took 20 mg of rimonabant, 36% had quit smoking. Of patients who took either placebo or 5 mg rimonabant, only 20% successfully quit. Further, of those patients who quit smoking, the ones taking either placebo or 5 mg rimonabant gained 84% more weight than those taking 20 mg rimonabant. Thus, rimonabant at 20 mg per day significantly increased the rate of successfully quitting smoking, and also greatly reduced post-smoking-cessation weight gain. (3)
Patients hit plateaus after about 34 weeks, when their weight loss ceased. If they stopped taking the drug, they gained back all they had lost, but the hope is that if people continue taking the drug indefinitely, they can maintain that weight loss and gain health benefits.(4)
RIO trial programme suggest rimonabant is well tolerated in long-term use. (1)
Some of the side effects you may encounter while using this drug include nausea, vomiting, diarrhea, mood swings, anxiety, you may become irritable, headaches, dizziness, depression (may become suicidal), trouble sleeping, you also may get nightmare. You may get symptoms that lead to psychosis and could lead to the use of anti-psychotic medication in order to improve. The only relatively common side effects most people encounter are mild GI side effects and dizziness. Most of the symptoms were experienced at the dose of 20mg/ed or more.
Ref.
(1) drugdevelopement-technology Sanofi-Aventis
(2) medicalnewstoday
(3) Richard N. Fogoros, M.D.
(4) Dr. F. Xavier Pi-Sunyer Columbia University
(5) Dr. Jean-Pierre Despres of Laval University