Rimonabant

Rimonabant (also known as SR141716; trade names Acomplia and Zimulti) is an anorectic anti-obesity drug originally approved in Europe in 2006. Developed by Sanofi-Aventis, Rimonabant was designed as a treatment to reduce appetite and aid in weight loss. However, it was withdrawn worldwide in 2008 due to serious psychiatric side effects and was never approved for use in the United States.^[1]^[2]

Mechanism of Action[edit]

Rimonabant is a selective inverse agonist of the CB₁ receptor, which is part of the endocannabinoid system that regulates appetite, mood, and energy balance. By blocking CB₁ receptors, Rimonabant reduces appetite and food intake. Research indicated that Rimonabant also affected the μ-opioid receptor, which may have contributed to both its effectiveness and side effects.^[3]

Development and Approval[edit]

Sanofi-Aventis discovered and developed Rimonabant, achieving approval from the European Commission on June 21, 2006. It was marketed as a prescription drug for patients with a BMI of over 30 kg/m² or over 27 kg/m² if associated with risk factors like type 2 diabetes or dyslipidaemia. However, approval requests in the United States were denied by the FDA, citing unresolved safety concerns.^[4]

Clinical Trials and Studies[edit]

Rimonabant's effectiveness and risks were assessed in several trials, including the RIO (Rimonabant In Obesity) trials. These studies showed significant weight loss and improvements in metabolic syndrome parameters. However, the trials also revealed notable psychiatric side effects, such as depression, anxiety, and suicidal ideation.^[5]

Adverse Effects and Safety Concerns[edit]

Rimonabant's side effects included psychiatric disorders in up to 10% of subjects, with suicidal ideation affecting around 1%. Additional common side effects were nausea, gastroenteritis, insomnia, muscle cramps, and fatigue. The European Medicines Agency recommended suspension due to these psychiatric risks, and sales were subsequently halted worldwide in 2008.^[6]

Withdrawal and Regulatory Actions[edit]

In October 2008, the European Medicines Agency (EMA) recommended suspension of Rimonabant, citing the risks of serious psychiatric side effects, including suicidal ideation. In 2009, the FDA reaffirmed its stance against approval. India also banned its manufacture and sale. Consequently, Rimonabant was withdrawn from all markets.^[7]

Pharmacodynamics and Chemistry[edit]

Rimonabant's action as an inverse agonist at the CB₁ receptor highlights its novel mechanism for obesity treatment. The compound also antagonizes the μ-opioid receptor, potentially enhancing side effects. The molecular structure of Rimonabant comprises several key functional groups, contributing to its biological activity.^[8]

Current Status[edit]

Rimonabant was first approved in Europe in 2006. However, it was withdrawn worldwide in 2008 due to serious psychiatric side effects. Rimonabant was never approved in the United States. Since its withdrawal, Rimonabant is not available for prescription. However, its mechanism of action continues to be studied for potential therapeutic uses, particularly in the treatment of addictions and metabolic disorders.

Future Perspectives and Research[edit]

Although withdrawn, Rimonabant's effects on the endocannabinoid system have informed ongoing research in obesity and metabolic disorders. Investigations into safer CB₁ antagonists or modulators continue. The knowledge gained from Rimonabant has also guided the development of alternative weight management strategies without associated psychiatric risks.^[9]

External links[edit]

EMA summary for Acomplia
FDA information on withdrawn anti-obesity drugs
Pubmed article: [1]

References[edit]

↑ Rimonabant(link). {{{website}}}. AdisInsight. Accessed 21 February 2017.
↑ "Rimonabant: From RIO to Ban".Journal of Obesity.2011;2011
432607.doi:10.1155/2011/432607.PMID:21773005.PMC:3136184.
↑ "Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action and unanswered questions".International Journal of Obesity.September 2009;33(9)
947–955.doi:10.1038/ijo.2009.132.PMID:19597516.
↑ , FDA Panel Rejects Drug for Obesity Full text, The New York Times, 14 June 2007,
↑ Acomplia EPAR(link). {{{website}}}. EMA. January 30, 2009. Accessed February 21, 2017.
↑ "Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial".Lancet.August 2010;376(9740)
517–523.doi:10.1016/S0140-6736(10)60935-X.PMID:20709233.
↑ Anti-obesity drug use suspended(link). {{{website}}}. 23 October 2008.
↑ "Studies on hindered phenols and analogues. Hypolipidemic and hypoglycemic agents".Journal of Medicinal Chemistry.February 1989;32(2)
421–428.doi:10.1021/jm00122a022.PMID:2913302.
↑ "Cannabinoid type 1 receptor antagonists for smoking cessation".The Cochrane Database of Systematic Reviews.March 2011;2011
CD005353.doi:10.1002/14651858.CD005353.pub4.PMID:21412887.

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[1] Rimonabant(link). {{{website}}}. AdisInsight. Accessed 21 February 2017.

[Sam2011rev-2] "Rimonabant: From RIO to Ban".Journal of Obesity.2011;2011
432607.doi:10.1155/2011/432607.PMID:21773005.PMC:3136184.

[3] "Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action and unanswered questions".International Journal of Obesity.September 2009;33(9)
947–955.doi:10.1038/ijo.2009.132.PMID:19597516.

[4] , FDA Panel Rejects Drug for Obesity Full text, The New York Times, 14 June 2007,

[EMAlabel-5] Acomplia EPAR(link). {{{website}}}. EMA. January 30, 2009. Accessed February 21, 2017.

[6] "Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial".Lancet.August 2010;376(9740)
517–523.doi:10.1016/S0140-6736(10)60935-X.PMID:20709233.

[7] Anti-obesity drug use suspended(link). {{{website}}}. 23 October 2008.

[8] "Studies on hindered phenols and analogues. Hypolipidemic and hypoglycemic agents".Journal of Medicinal Chemistry.February 1989;32(2)
421–428.doi:10.1021/jm00122a022.PMID:2913302.

[9] "Cannabinoid type 1 receptor antagonists for smoking cessation".The Cochrane Database of Systematic Reviews.March 2011;2011
CD005353.doi:10.1002/14651858.CD005353.pub4.PMID:21412887.

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