Rimonabant—A Selective CB1 Antagonist

Boyd, Steven T.; Fremming, Brad Allen

doi:10.1345/aph.1e499

Cited by 105 publications

(86 citation statements)

References 23 publications

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“…16 To date, results have been published relating to the effects of 12 months of treatment with rimonabant in two of these studies -RIO-Europe and RIO-Lipids. 9,19 The RIO-Europe study recruited 1507 patients, characterised by obesity (a BMI of ≥30kg/m 2 ), or the metabolic syndrome (a BMI >27kg/m 2 plus treated or untreated dyslipidaemia, hypertension or both), and randomised them to treatment with either rimonabant 5mg or 20mg once daily or placebo, as adjunct to a mild hypocalorific diet (600kcal per day deficit).…”

Section: Clinical Studies In Obesitymentioning

confidence: 99%

“…16,23 During the clinical development of rimonabant, there has been close scrutiny of the tolerability and safety profile of this novel CB1 inhibitor. Evidence from shortterm clinical studies to date, in which patients have received daily doses of up to 20mg rimonabant for over 1 year, is that the treatment is well tolerated.…”

Section: Safety Profile Of Rimonabantmentioning

confidence: 99%

“…Evidence from shortterm clinical studies to date, in which patients have received daily doses of up to 20mg rimonabant for over 1 year, is that the treatment is well tolerated. 9,10,16,19,22 The most frequent adverse events seen to date are nausea (in RIOLipids 12.7 per cent for 20mg rimonabant vs 3.2 per cent in placebo patients), dizziness (10.4 per cent rimonabant 20mg vs 6.7 per cent placebo) and upper respirator y tract infections (STRATUS-US 15.7 per cent rimonabant 20mg and 9.2 per cent placebo). 16 In all trials these effects were generally found to be mild and transient, and patient drop-out rates were similar in the placebo and rimonabant arms.…”

Section: Safety Profile Of Rimonabantmentioning

confidence: 99%

“…The drug also shows activity at peripheral CB1 receptors, where it appears to affect metabolism in adipose tissue. 16 Evidence from clinical studies suggests that rimonabant is a promising new drug that appears to promote weight reduction and to tackle other cardiovascular and metabolic risk factors seen in centrally obese subjects and patients described as having the metabolic syndrome. The agent's additional ability to assist with smoking cessation singles it out as having unique properties in controlling risk factors in patients at high risk of cardiovascular and metabolic morbidity and mortality.…”

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Rimonabant in the management of cardiovascular risk

Barnett

2006

Future Prescriber

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4 F U T U R E P R E S C R I B E R V O L 7 ( 2 )w w w . e s c r i b e r . c o m D R U G P R O F I L E r i m o n a b a n tRimonabant in the management of cardiovascular risk Figure 1. Obesity poses one of the greatest modern healthcare challenges.SPL glucose level greater than 5.5mmol/l. 5 It has been argued that unless there are effective population-level inter ventions to reduce obesity on a consistent and regular basis, the steady rise in life expectancy that has been a feature of the past century could come to an end. 6 For obese subjects, weight loss of between 5-10 per cent can significantly improve risk factors for obesity-related diseases and delay, or prevent, development of type 2 diabetes. 7 Achieving and maintaining weight loss through lifestyle changes alone is difficult for many overweight people and, while behavioural and cognitive treatments can work for some individuals, these approaches have not had broad success. Despite many efforts to find adjunctive treatments to support obese patients in achieving clinically meaningful weight loss, there have, until recently, been few successes in this therapeutic area. 3,7 The history of weight-loss medications includes the use and abuse of amphetamines and a host of drugs withdrawn due to safety concerns. 7 Many potential therapies designed to promote weight loss have been plagued with unwanted side-effects and poor safety profiles. The result is that there are now only two widely approved adjunctive therapies for obesity management -sibutramine (a centrally-acting noradrenaline and serotonin reuptake inhibitor) and orlistat (an inhibitor of gastric and intestinal lipase). THE CANNABINOID SYSTEM: A NEW THERAPEUTIC TARGET IN OBESITY CONTROLRecent research has identified the endocannabinoid system as playing a crucial role in the control of food intake and energy balance in humans. This has led to interest in pharmacological manipulation of this system to induce weight loss and improve the metabolism of carbohydrates and lipids in obese subjects. [8][9][10] The endocannabinoid system consists of G1/0-protein-coupled CB1 receptors (which are expressed in several areas of the brain, in the autonomic nervous system and in peripheral organs such as liver, muscle, the gastrointestinal tract and adipose tissue) 11 and a family of locally produced, short-lived endogenous agonists for these receptorsthe endocannabinoids. 9,10 In recent years, a growing body of evidence has shown that stimulation of central CB1 receptors in the hypothalamus by endocannabinoid moieties can provoke food intake, even in satiated animals, and it has also been demonstrated that CB1 stimulation in fat cells promotes lipogenesis and inhibits the production of adiponectin, a cytokine with antidiabetic and antiatherosclerotic properties. 9 Central CB1 receptors also appear to be expressed in the brain in 'reward circuits' of the mesolimbic system that are activated by psychostimulants such as nicotine and drugs associated with the phenomena of habituation and dependence. 12 RIMONABANT: DEVELO...

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Section: Clinical Studies In Obesitymentioning

confidence: 99%

Section: Safety Profile Of Rimonabantmentioning

confidence: 99%

Section: Safety Profile Of Rimonabantmentioning

confidence: 99%

mentioning

confidence: 99%

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Rimonabant in the management of cardiovascular risk

Barnett

2006

Future Prescriber

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“…It is also under investigation for treating drug addiction (Beardsley and Thomas 2005), and additional possible uses have been proposed (Bifulco et al 2007). The experimental effects of rimonabant on food intake, addiction, and other effects in the central nervous system have recently been reviewed (Boyd and Fremming 2005;Fowler 2005;Shire et al 1999). In this manuscript we systematically review rimonabant effects outside the central nervous system.…”

Section: Introductionmentioning

confidence: 99%

Prejunctional and peripheral effects of the cannabinoid CB1 receptor inverse agonist rimonabant (SR 141716)

Diepen

Schlicker

Michel

2008

Naunyn-Schmied Arch Pharmacol

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Rimonabant is an inverse agonist specific for cannabinoid receptors and selective for their cannabinoid-1 (CB 1 ) subtype. Although CB 1 receptors are more abundant in the central nervous system, rimonabant has many effects in the periphery, most of which are related to prejunctional modulation of transmitter release from autonomic nerves. However, CB 1 receptors are also expressed in, e.g., adipocytes and endothelial cells. Rimonabant inhibits numerous cardiovascular cannabinoid effects, including the decrease of blood pressure by central and peripheral (cardiac and vascular) sites of action, with the latter often being endothelium dependent. Rimonabant may also antagonize cannabinoid effects in myocardial infarction and in hypotension associated with septic shock or liver cirrhosis. In the gastrointestinal tract, rimonabant counteracts the cannabinoid-induced inhibition of secretion and motility. Although not affecting most cannabinoid effects in the airways, rimonabant counteracts inhibition of smoothmuscle contraction by cannabinoids in urogenital tissues and may interfere with embryo attachment and outgrowth of blastocysts. It inhibits cannabinoid-induced decreases of intraocular pressure. Rimonabant can inhibit proliferation of, maturation of, and energy storage by adipocytes. Among the many cannabinoid effects on hormone secretion, only some are rimonabant sensitive. The effects of rimonabant on the immune system are not fully clear, and it may inhibit or stimulate proliferation in several types of cancer. We conclude that direct effects of rimonabant on adipocytes may contribute to its clinical role in treating obesity. Other peripheral effects, many of which occur prejunctionally, may also contribute to its overall clinical profile and lead to additional indications as well adverse events.

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Cannabinoid type 1 receptor antagonists (rimonabant) for smoking cessation

Ussher

2007

Cochrane Database of Systematic Reviews

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Rimonabant—A Selective CB1 Antagonist

Cited by 105 publications

References 23 publications

Rimonabant in the management of cardiovascular risk

Rimonabant in the management of cardiovascular risk

Prejunctional and peripheral effects of the cannabinoid CB1 receptor inverse agonist rimonabant (SR 141716)

Cannabinoid type 1 receptor antagonists (rimonabant) for smoking cessation

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