Drugs for relapse prevention of alcoholism: ten years of progress.

Multiple neurochemical pathways are involved in mediating craving and relapse to alcohol. Opioidergic and glutamatergic systems have a key role in alcoholism, as demonstrated by the clinically effective compounds naltrexone and acamprosate acting through these systems. The dopaminergic system has long featured in alcoholism research; hitherto disappointing results from clinical studies could improve following the discovery that dopamine D3 receptor antagonism produces consistent and robust results in preclinical studies. Corticotropin-releasing factor signalling and the endocannabinoid system integrate stress-related events and thereby mediate relapse behaviour. Overall, these new targets have yielded several compounds that are undergoing clinical testing. However, the heterogeneity in treatment response makes it necessary to characterize genetic and protein markers and endophenotypes for individualized pharmacotherapy.