Will the new CB₁ cannabinoid receptor antagonist SR-147778 have advantages over rimonabant?

Abstract

Obesity and alcoholism are two common modern-day diseases. The cannabinoid CB1 receptor antagonist rimonabant is in Phase III clinical trial for the treatment of obesity with preliminary results showing that it decreases appetite and body weight. Animal studies have shown that rimonabant is effective in the treatment of alcoholism. SR-147778 is a new potent and selective CB1 receptor antagonist. In animals, SR-147778 has been shown to inhibit CB1 receptor-mediated hypothermia, analgesia and slowing of gastro-intestinal transit. In rats trained to drink sucrose, the oral administration of SR-147778 3 mg/kg, before the presentation of sucrose, decreased the consumption of sucrose. SR-147778 3mg/kg also reduced spontaneous feeding in rats deprived of food and also in non-deprived rats. In Sardinian alcohol--preferring (sP) rats, in the alcohol-naive state, SR-147778 slowed the development of a preference for alcohol. In alcohol-experienced sP rats SR-147778 (2.5, 5 and 10 mg/kg p.o.) reduced the alcohol intake. When alcohol-experienced sP rats are deprived of alcohol for 15 days, there is a large intake of alcohol on reintroduction of alcohol, and this response was almost abolished by treatment with SR-147778. From the preclinical studies published to date, there is no obvious major point of difference between rimonabant and SR-147778, and both are promising agents for the treatmentof obesity and alcoholism.

• alcoholism
• CB1 receptor antagonist
• CB1 receptor
• obesity
• rimonabant
• Sardinian alcohol-preferring rats
• SR-147778