Pharmacological profile and clinical findings of nalmefene (Selincro ® ) for reducing alcohol consumption in patients with alcohol dependence

Nalmefene (Selincro((R))), an opioid receptor modulator, is approved in Japan, the European Union, and other countries for reducing alcohol consumption in patients with alcohol dependence. This article reviews the efficacy and safety of as-needed use of nalmefene in the treatment of alcohol dependence, as well as summarizing its pharmacological properties. Ethanol increases the release of endogenous opioids, such as beta-endorphin, a mu-opioid receptor agonist; and dynorphin, a kappa-opioid receptor agonist. Preclinical data suggest that nalmefene acts as an antagonist at the mu-opioid receptor and a partial agonist at the kappa-opioid receptor, and reduces ethanol self-administration in ethanol-dependent and ethanol-non-dependent rats. Nalmefene counters alcohol-induced dysregulation of the beta-endorphin/mu-opioid receptor and the dynorphin/kappa-opioid receptor systems. In a multicenter, randomized, double-blind, phase 3 study of as-needed use of nalmefene combined with psychosocial support in alcohol-dependent Japanese patients with at least high drinking risk level, compared with placebo, nalmefene 10 mg and 20 mg significantly reduced the number of heavy drinking days and total alcohol consumption at week 12. In the 24-week treatment period, treatment-emergent adverse events occurred in >/=5% of patients in either the nalmefene 10 mg or 20 mg group and at least twice as often as in the placebo group were nausea, dizziness, somnolence, vomiting, insomnia, decreased appetite, constipation, malaise, and palpitations. Most adverse events were mild or moderate in severity. In conclusion, as-needed use of nalmefene provides a new concept for the treatment of alcohol dependence: namely, "reduction of alcohol intake".