Antiobesity agent - taranabant

The cannabinoid CB1 receptor is implicated in the control of eating and energy use in the body - hence the common phenomenon of "getting the munchies" after smoking cannabis.

?Sanofi-aventis's drug rimonabant (Acomplia) was designed as an inverse agonist for this receptor, and has been shown to decrease the intake of food and increase the expenditure of energy. It is marketed in Europe as an aid to weight loss, although there have been some concerns about side-effects and it has not been given US FDA approval.

Another inverse agonist of the CB1 receptor, taranabant, is being developed by Merck & Co.¹ In one randomised, double-blind, four period crossover trial, 17 overweight or moderately obese male subjects were given single doses of 4 or 12mg taranabant, 30mg sibutramine or placebo.² Indirect calorimetry was used to evaluate their resting energy expenditure over the five hours after dosing, and again after 24 hours. Peak geometric mean ratios for the two doses of taranabant and rimonabant compared with placebo were 1.02, 1.06 and 1.03 respectively; it was well tolerated.

Its effect on food intake has also been investigated.³ A total of 36 overweight or obese male subjects were given a similar dosing regimen to the previous trial. They were given meals that were about five times larger than a normal meal 3, 10, 13 and 24 hours after dosing, and were allowed to eat as much as they wanted.

There was a mean reduction of energy intake of 3%, 22% and 12% for the different doses respectively compared with placebo over the 24-hour period. The higher dose of rimonabant gave the lowest energy intake at all four meals, and there was no significant effect with the lower dose.

Various other trials are under way, including Phase II and Phase III studies in obese and overweight subjects, and also in patients with Type II diabetes. It is also being investigated as a possible aid to smoking cessation.