AimsReducing alcohol consumption is one treatment approach for alcohol‐dependent patients. This study compared nalmefene 20 mg and 10 mg with placebo, combined with psychosocial support, in alcohol‐dependent Japanese patients with a high or very high drinking risk level (DRL).MethodsThis was a multicenter, randomized, double‐blind, phase 3 study conducted in alcohol‐dependent patients with a high or very high DRL. Patients were randomized to 24 weeks of treatment with as‐needed nalmefene 20 mg, 10 mg, or placebo with psychosocial support. The primary endpoint was change in heavy drinking days (HDD) from baseline to week 12. A key secondary endpoint was the change in total alcohol consumption (TAC) from baseline to week 12.ResultsAt week 12, 234, 206, and 154 patients who received placebo, nalmefene 20 mg, and 10 mg were included in the primary endpoint analysis. Compared with placebo, nalmefene was associated with significant reductions in HDD at week 12 (difference in 20 mg group, −4.34 days/month; 95% confidence interval [CI]: −6.05 to −2.62; P < 0.0001; difference in 10 mg group, −4.18 days/month; 95%CI: −6.05 to −2.32; P < 0.0001), as well as a significant reduction in TAC at week 12 (P < 0.0001). The incidence of treatment‐emergent adverse events was 87.9%, 84.8%, and 79.2% in the groups receiving nalmefene 20 mg, 10 mg, and placebo, respectively. These events were mostly of mild or moderate severity.ConclusionsNalmefene 20 mg or 10 mg effectively reduced alcohol consumption and was well tolerated in alcohol‐dependent patients with a high or very high DRL.

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Together with our previous study indicating that the nucleus accumbens and the ventral tegmental area are partially involved in the DS effects of nicotine, the present study suggests that mPFC is primarily involved in the DS effects of nicotine.

ABSTRACT-To examine the effects of drugs on short-term memory in animals, the delayed discri mination experiment in rats and the delayed matching to sample experiment in rhesus monkeys were conducted. Nicotine at 0.125 mg/kg, s.c. in rats and at 0.5 mg/kg, s.c. in monkeys increased the per centages of correct choices. Scopolamine at 0.06-0.12 mg/kg, s.c. in rats and at 0.015 mg/kg, s.c. in monkeys decreased the percentages of correct choices. However, supposedly memory-specific, delay time-dependent disruptive effects by scopolamine were found only in monkeys. Diazepam at 0.5-2 mg/kg, s.c. did not change the correct choices in rats. However, diazepam at 1-4 mg/kg, i.g. de creased the correct choices in monkeys regardless of the delay time. Chlorpromazine at 0.25-1.5 mg/kg, s.c. showed inconsistent effects in rats. In monkeys, chlorpromazine at 0.25-0.5 mg/kg, s.c. had no effect. These results suggested that using both rats and monkeys would be useful for evaluating the effects of drugs on memory.