Rimonabant

(USAN, rINN)
Rimonabant Chemical formula
Synonyms: Rimocaban; Rimonabantum; SR-141716. 5-(p-Chlorophenyl)-1(2,4-dichlorophenyl)-4-methylN-piperidinopyrazole-3-carboxamide.
Cyrillic synonym: Римонабант.

💊 Chemical information

Chemical formula: C22H21Cl3N4O = 463.8.
CAS — 168273-06-1 (rimonabant); 158681-13-1 (rimonabant hydrochloride).
ATC — A08AX01.
ATC Vet — QA08AX01.

💊 Profile

Rimonabant is a selective cannabinoid type-1 receptor antagonist used as an adjunct to diet and exercise for the treatment of obese patients (BMI ≥ 30 kg/m2), and also for overweight patients (BMI > 27 kg/m2) who have associated risk factors such as type 2 diabetes mellitus or dyslipidaemia. It is given orally in doses of 20 mg daily before breakfast. However, following concern about psychiatric reactions marketing of rimonabant was suspended in Europe in October 2008. Nausea, anxiety, and dizziness occur commonly with rimonabant. Depressive symptoms have also occurred and rimonabant should not be given to patients with major depression or to those being treated with antidepressants; it is also not recommended in patients with other uncontrolled serious psychiatric disorders. Since rimonabant is metabolised by the liver, caution is advised in patients with moderate hepatic impairment. Licensed product information does not recommend its use in patients with severe hepatic or renal impairment because of lack of data in these patient groups. Plasma concentrations of rimonabant are increased when given with ketoconazole; other CYP3A4 inhibitors might have the same effect. Rimonabant is also being investigated as an aid for smoking cessation. Rimonabant is a selective cannabinoid type-1 receptor antagonist that reduces the overactivity of the endocannabinoid (endogenous cannabinoid) system. Studies of rimonabant in vitro and in animals have shown that it inhibits the proliferation and maturation of adipocytes, improves lipid and glucose metabolism, and regulates food intake and energy balance.1,3,4 Four large multicentre randomised controlled studies have been carried out to examine the effects of rimonabant in obesity (RIO) in conjunction with a mildly hypocalorific diet (deficit of about 600 kcal/day),6-9 and all studies showed that rimonabant was of benefit when given at a dose of 20 mg daily. A significant decrease in body-weight and waist circumference was reported from the RIO-Europe study6 over 1 year, although results from the RIO-North America study7 conducted over 2 years were more modest; both studies also showed improvement in cardiovascular risk factors. The RIO-Lipids study8 examined the effects of rimonabant over 1 year in overweight or obese patients with untreated dyslipidaemias and noted improvement in several metabolic risk factors as well as weight loss. Similar results including improvement in plasma-glucose concentrations (as indicated by glycosylated haemoglobin measurements) were obtained in overweight or obese patients with type 2 diabetes mellitus given rimonabant over 1 year in the RIO-Diabetes study.9 Meta-analysis10 and systematic review11 of the 4 studies in the RIO-programme agreed that rimonabant produced statistically greater weight loss than placebo, although some problems with methodology were noted. Since no follow-up data were reported, no conclusion could be reached about weight regain.10 Of particular concern was the increase in incidence of psychiatric adverse effects such as depression and anxiety in the treatment group.10 Rimonabant is also being studied as an aid to smoking cessation but a systematic review12 of randomised controlled studies concluded that although rimonabant 20 mg daily may be of benefit in stopping smoking, the evidence in maintaining abstinence is inconclusive.
1. Boyd ST, Fremming BA. Rimonabant—a selective CB1 antagonist. Ann Pharmacother 2005; 39: 684–90
2. Gelfand EV, Cannon CP. Rimonabant: a cannabinoid receptor type 1 blocker for management of multiple cardiometabolic risk factors. J Am Coll Cardiol 2006; 47: 1919–26
3. Henness S, et al. Rimonabant. Drugs 2006; 66: 2109–19
4. Patel PN, Pathak R. Rimonabant: a novel selective cannabinoid1 receptor antagonist for treatment of obesity. Am J Health-Syst Pharm 2007; 64: 481–9
5. Xie S, et al. The endocannabinoid system and rimonabant: a new drug with a novel mechanism of action involving cannabinoid CB receptor antagonism — or inverse agonism — as potential obesity treatment and other therapeutic use. J Clin Pharm Ther 2007; 32: 209–31
6. Van Gaal LF, et al. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 2005; 365: 1389–97. Correction. ibid. 366: 370
7. Pi-Sunyer FX, et al. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA 2006; 295: 761–75
8. Després J-P, et al. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005; 353: 2121–34
9. Scheen AJ, et al. RIO-Diabetes Study Group. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 2006; 368: 1660–72
10. Christensen R, et al. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet 2007; 370: 1706–13
11. Curioni C, André C. Rimonabant for overweight or obesity. Available in The Cochrane Database of Systematic Reviews; Issu
4. Chichester: John Wiley; 2006 (accessed 14/02/08)
12. Cahill K, Ussher M. Cannabinoid type 1 receptor antagonists (rimonabant) for smoking cessation. Available in The Cochrane Database of Systematic Reviews; Issu
4. Chichester: John Wiley; 2007 (accessed 14/02/08).

💊 Preparations

Proprietary Preparations

Arg.: Acomplia; Resibant; Cz.: Acomplia†; Zimulti; Fr.: Acomplia†; Gr.: Acomplia† Port.: Zimulti; UK: Acomplia†.
Published May 08, 2019.