Opioid Antagonists

Opioid antagonists are a class of compounds that selectively bind to opioid receptors.  These compounds inhibit opioid receptor activation by blocking the actions of both exogenous opioids (analgesics such as morphine and illicit opioids such as heroin) and endogenous opioid-like peptides (enkephalins, endorphins, dynorphins). Thus, opioid antagonists can regulate the reward circuitry by reducing/inhibiting behaviors (e.g. craving, reward) triggered by opioid receptor activation produced by both substance misuse. Because both endogenous opioid-like peptides and opioid drugs modulate dopamine release (through opioid receptor activation), opioid antagonists can also help manage dopamine-mediated behaviors such as increased reward expectancy.

Three opioid antagonists have been approved by the United States Food and Drug Administration (FDA): naltrexone, naloxone and nalmefene (now only available in Europe).  Naltrexone is administered as an oral tablet or by depot injection to treat alcohol and opioid use disorders.  Naloxone is currently approved for the treatment of opioid overdose, and is administered either by injection or nasal spray.  NARCAN® Nasal Spray, developed by Opiant and marketed by our partner Adapt, is the only FDA approved intranasal formulation of naloxone.  Currently, nalmefene is formulated as an oral tablet for alcohol dependence in Europe.

Treatment with opioid antagonists blocks opioids in critical brain regions, reducing dopamine, and therefore reward

Reward Circuitry Addictive Disorder
– excess dopamine present

Reward Circuitry Opioid Antagonist Treatment
– restoring excess dopamine to normal levels