Drugs Currently on the Market for the Treatment of Addiction – Preclinical Background

Alcohol and Opioids

• Naltrexone (Revia, Vivitrol). Naltrexone, a competitive opioid antagonist, has high affinity for the μ opioid receptor and is less potent at the δ and κ receptors. Naltrexone has long been known to decrease alcohol consumption in animal models. In an early study, intramuscular administration of naltrexone decreased intravenous alcohol self-administration in rhesus monkeys. Subsequently, naltrexone was shown to decrease alcohol drinking and self-administration in various animal models. Brain sites particularly effective in the actions of opioid antagonists on alcohol self-administration include the nucleus accumbens, central nucleus of the amygdala, and ventral tegmental area. Human studies have suggested that endogenous opioids may be involved in the direct reinforcing effects of alcohol, and opioid antagonists may blunt the reinforcing effects of alcohol and blunt the urge to drink elicited by the presentation of alcohol-related cues in alcohol-dependent subjects. Naltrexone has been shown to reduce craving for alcohol in human laboratory studies, and this effect may be related to its ability to activate the hypothalamic–pituitary–adrenal axis. Similar results have been observed in a rat model of cue-induced reinstatement, in which re-exposure to an olfactory stimulus that signaled the availability of alcohol self-administration produced strong reinstatement of responding after extinction. This reinstatement was blocked by systemic administration of naltrexone (for further reading, see Unterwald, 2008). Naltrexone completely blocks the reinforcing and dependence-inducing effects of opioids in animal models. In an actively opioid-dependent animal (or human), naltrexone will “precipitate” opioid withdrawal ).

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