Rimonabant (also known as SR141716; trade names Acomplia,
Bethin, Monaslim, Remonabent, Riobant, Slimona,
and Riomont) is an anorectic
antiobesity drug that has
been withdrawn from the market. It is an inverse agonist for the cannabinoid
Its main effect is reduction in appetite.
Rimonabant was the first selective CB1 receptor blocker to be approved for
use anywhere in the world. In Europe, it was indicated for use in
conjunction with diet and exercise for patients with a body mass index greater than 30 kg/m², or patients with a BMI
greater than 27 kg/m² with associated risk factors, such as type 2 diabetes or dyslipidaemia. In the UK, it was available
beginning in July 2006. As of 2008, the drug was available in 56
countries. On 23 October 2008, the European Medicines Agency (EMEA)
issued a press release stating its Committee for Medical Products for
Human Use (CHMP) had concluded the benefits of Acomplia no longer
outweighed its risks, and subsequently recommended the product be
suspended from the UK market. Sanofi-Aventis later
released a press statement stating the drug had been suspended.
Approval of the drug was officially withdrawn by the EMEA on 16 January
- 1 History
- 2 Side effects
- 3 Other uses
- 4 Reaction
- 5 References
The French pharma firm Sanofi-Aventis disclosed a
complete response to the FDA's approvable letter was submitted on 26
October 2006, triggering a Class I (two-month) or Class II (six-month)
review process. On 13 June 2007, FDA's Endocrine and Metabolic Drugs
Advisory Committee (EMDAC) concluded the French manufacturer
Sanofi-Aventis failed to demonstrate the safety of rimonabant and voted
against recommending the anti-obesity treatment for approval.
Subsequently, Sanofi-Aventis announced it was suspending the new drug
application (NDA) for rimonabant, and that it would resubmit an
application at some point in the future.
On 21 June 2006, the European Commission approved the sale of rimonabant in
the then-25-member European Union. Sanofi announced the first country in
which Acomplia would be sold was the United Kingdom as a prescription drug. Sales began in July
2006. Sanofi also announced it projected that the drug would be sold
shortly thereafter in Denmark, Ireland,
It was expected in Belgium
in 2007. Ordinary obesity would, according to official medical
recommendations, not be enough to acquire the prescription in Sweden;
there would be additional requirements concerning abnormal blood lipid
The EU's approval was not a blanket approval, nor did it approve
Acomplia for nonobesity-related problems, such as smoking cessation, although off-label
use of the drug was still possible. The approval was, in
combination with diet and exercise, for the treatment of obese patients (BMI greater than or equal to 30), or overweight patients (BMI
greater than 27) with associated risk factors, such as type 2 diabetes or dyslipidaemia.
Shortly after market introduction, press reports and independent
studies suggested side effects occurred more intensely and more commonly
than shown by the manufacturer in their clinical studies. Resulting
from drug actions at CB1 receptors in the brain, reports of severe
depression and suicidal thoughts are frequent.
As CB1 receptors are fairly ubiquitous throughout the central nervous
system, it is not currently understood where exactly the inverse agonist
is acting to cause these side-effects.
On 15 June 2007, BBC News reported
a 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.
Rimonabant may also be found to be effective in assisting some
smokers to quit smoking. Sanofi-Aventis 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-Aventis that, without additional studies,
rimonabant cannot be approved in the United States for smoking cessation
therapy. According to a Cochrane review in 2007, rimonabant
"may increase the odds of quitting approximately 11/2-fold".
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.
Tetrahydrocannabinol (THC) is known to impair short-term memory. It was therefore hypothesised that
rimonabant may improve short-term memory. Indeed, in animal studies, it
significantly improved the performance of rats to encode information in
the short-term memory.
of cannabis effects
Rimonabant reduces voluntary wheel running in laboratory mice.
Rimonabant can be synthesized as follows: