Accomplia - the next Vioxx?

Obesity is big business, if you'll pardon the pun. In the US especially, but all over the world, people are getting fatter and fatter on cheap and empty calories, and that brings with it a whole wealth of health problems. Obviously, if we all ate less and exercised more, we'd lose the weight and live longer, but it's not that easy. Sugar is almost an addictive substance, and exercise is hard work. Which is why drug companies are throwing their research weight behind pharmacological solutions. Wouldn't it be great if you could just take a pill to keep the weight off?

In fact, this used to be the case. Back in my Grandparents' day, housewives would think nothing of taking a week-long course of dexedrine or another amphetamine, and working off that excess fat with a bout of heavy housework. Those days passed, but they might be on their way back. One such anti-obesity drug is rimbonant (Accomplia), from Sanofi-Aventis. This drug works by blocking one of the two endogenous receptors for cannabinoids, the CB1 receptor. As you probably know, cannabis stimulates appetite, through activation of CB1 receptors in the brain. Blocking CB1 receptors with rimbonant has the opposite effect, inhibiting appetite. So far so good.

Right up until I discovered I'd previously encountered rimbonant, during my PhD. Back then, it was just known as SR141716A, and as a handy research tool for blocking CB1 receptors in experiments. My research was on vasodilator pathways, and how the body goes about relaxing blood vessels. This is a pretty important function that you'd be in big trouble without, and there is a certain redundancy built in. One of the pathways that controls vasodilation, at least in and around the gut, called EDHF, was blocked in our experiments by, yes you guessed it, SR141716A.

Just for a bit of context, another one of the pathways I focused on was COX-2, and we all know what happened with COX-2 inhibitors and the cardiovascular system. Now, I'm not claiming that rimbonant is the the next Vioxx , but at the same time I have to admit I'm wary about potentially interfering with vasodilation in obese patients, many of whom will likely have atherosclerosis and other conditions associated with metabolic syndrome. Derek Lowe, over at In the Pipeline wonders if there's something lurking in rimbonant's cupboard. He isn't the only one.