URB447 is a mixed central cannabinoid (CB1) receptor antagonist/peripheral cannabinoid (CB2) receptor agonist with IC50 values of 313 and 41 nM, respectively. At 20 mg/kg delivered intraperitoneally to ob/ob mice and Swiss mice, URB447 reduces food intake and body-weight gain with an efficacy comparable to rimonabant, which is an inverse agonist for the CB1. Marketed as an anti-obesity drug and appetite suppressant, rimonabant was subsequently suspended from distribution due to serious psychiatric side effects attributed to its indiscriminate activity on CB1 receptors in the central nervous system (CNS). Unlike rimonabant, URB447 does not penetrate the blood-brain barrier (to antagonize CB1 receptors in the CNS); instead, it appears to selectively block peripheral CB1 receptors such as those located in the gastrointestinal tract.
