Russ McGillivray

Natural Products Chemistry

Rimonabant: Another Marijuana Virtue

1.      Rimonabant is a synthetic analog of TetraHydroCannabinol, which differs in it structure so, that it acts as a central cannabinoid (CB1) antagonist in the mid-brain.  Rather than natural cannabinoids produced in the body, or exogenous ones, both which bind and enforce a positive signal in the receptors, Rimonabant (SR141716) binds to the same receptor and sends a negative signal.  The structure of Rimonabant was not specifically listed, but chances are the molecule is quite similar to the common Delta – 9 THC which is C21H302O.  THC contains a monoterpene (C10) unit, attached to a phenolic ring with a C5 alkyl chain.  Rimonabants structure and formula probably is similar, but rather than activating CB receptor to stimulate appetite in the hypothalamus, Rimonabant stops these receptors from sending such signals.  The source of the natural product THC is the Cannabis Sativa herb.

2.      Rimonabant was discovered only a few years ago, by a French company named Sanofi – Synthelabo.  Gerard Le Fur is currently the head of production and testing of Rimonabant in Sanofi – Synthelabo, and hopes that the drugs will have passed all clinical trails and be on the market for smoking cessation and weight loss by early 2004.  This is sort of a wonder drugs in that it can be used as a weight loss drug and a smoking cessation drug, and since most people gain weight when they quite smoking, this drug may prove to be very beneficial.  Rimonabant has also been shown to inhibit the mental need for alcohol, and should begin testing of it effectiveness soon.  Rimonabant is the first of its kind of drugs; central cannabinoid antagonist.

3.      Rimonabant began is clinical phase III tests in August of 2002 and are still in progress now.  The results look promising, but the long-term results are still unknown.  In earlier clinical tests, Rimonabant showed a 200% in smoking cessation over placebo in a group of 180, and a 2.5% weight loss versus the 2.5% weight gain by placebo.  The results have shown that Rimonabant has shown sinificant benefit as a weight loss and smoking cessation drug.  The drugs is currently being tested for its efficiency as a long-term weight loss aid now.  Sales are predicted to be 1.4 billion by the year 2010.  The mechanism of the drug is to turn off the cannabinoid or hunger receptors in the hypothalamus by antagonizing the receptors. 

4.      Today, smoking and obesity are the two overwhelming leaders in the cause for preventable disease in the United States and in the world.  Obesity has increased over 75% in the last two decades, and the increase in heart disease, stroke and diabetes are there to back up the health effects associated with obesity.  Developing a drug, which may contibute significantly to the decrease in tobacco consumption and to help achieve a healthy weight, is a responsible investment.  This drug could save lives and save pocket books.

5.      Sources:

www.nih.gov

www.en.sanofi-synthelabo.com/rd/strategy/p_rd_strategy_explorating.asp

www.planetsave.com

Dewick, M. Paul.  Medicinal Natural Products. A Biosynthetic Approach. Second Edition. John Wiley & Sons, LTD., West Sussex, England, 2002.  Pages 84-87.