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The 380 mg dosage reduced the number of heavy drinking days by 25%, which was significantly better than placebo. Although the naltrexone 190 mg dosage reduced heavy drinking days by 17%, it was not significantly better than placebo. (b) Nalmefene: Mason and colleagues (1994) found that nalmefene, another opioid antagonist, at a dosage of 40 mg/day, was superior to nalmefene 10 mg/day or placebo in preventing relapse to heavy drinking. Mason et al. (1999) subsequently found no difference between nalmefene 20 mg/day and 80 mg/day. However, when grouped together, the nalmefene-treated subjects were significantly less likely to relapse to heavy drinking than was the placebo group. In a 12-week, multisite study in recently abstinent outpatient alcoholics (Anton et al., 2004), participants received Olaparib ic50 5 mg, 20 mg, or 40 mg of nalmefene or placebo daily. All groups reduced the frequency of heavy drinking days equally. Recently, based on the results of three European studies, the European Medicines Agency approved nalmefene 18 mg for as-needed treatment to reduce heavy drinking in alcohol-dependent patients. In the first of these studies, Mann et al. (2013) randomly assigned 598 subjects to 6 months of treatment with nalmefene or placebo. Nalmefene treatment http://www.selleckchem.com/products/Y-27632.html significantly reduced heavy drinking by 2.3 days per month and total alcohol consumption by about one standard drink per day more than placebo treatment. In a 6-month study of 718 patients with alcohol dependence (Gual et al., 2012), nalmefene-treated subjects reported a significantly greater reduction in the number of bepotastine heavy drinking days and total alcohol consumption than the placebo group. In a 12-month study of 665 patients (van den Brink et al., 2012), nalmefene reduced the number of heavy drinking days and total alcohol consumption throughout the treatment period. Except for the study midpoint, this reduction was statistically significant. Acamprosate. In 2004, the FDA approved the amino acid derivative acamprosate to treat alcohol dependence, based on the results of three pivotal European studies (reviewed in Kranzler and Gage, 2008). Acamprosate appears to exert its effects through a weak antagonism of N-methyl-D-aspartate (NMDA) receptor activity and inhibition of the metabotropic glutamate receptor 5 (Blednov and Harris, 2008; Mann et al., 2008). In a meta-analysis of 24 RCTs enrolling a total of 6,915 subjects, mostly participants in the European studies conducted by the company that owns the drug (R?sner et al. 2010a), acamprosate significantly reduced the risk of drinking and significantly increased the duration of abstinence. However, in four large studies, including two multicenter trials in the United States (Anton et al., 2006; Mason et al., 2006), a European study (Mann et al.