Will the new CB_1 cannabinoid receptor antagonist SR-147778 have advantages over rimonabant?

摘要

Obesity and alcoholism are two common modern-day diseases.The cannabinoid CB,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 CB,receptor antagonist.In animals,SR-147778 has been shown to inhibit CB,receptor-mediated hypothermia,analgesia and slowing of gastrointestinal 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 3 mg/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 treatment of obesity and alcoholism.