The Sound of Evolution
Naltrexone
Mechanism of action:
Naltrexone is an opioid receptor antagonist. Naltrexone is characterized by strong μ-opioid receptor antagonism, along with κ- and δ-opioid receptor antagonism, and has a long duration of action. After naltrexone antagonizes the μ-opioid receptor, adenylyl cyclase is no longer inhibited, cAMP levels rise, calcium channels resume normal opening, synaptic vesicles release neurotransmitters again, and excitatory transmission is restored. Potassium efflux is also reduced, allowing neurons to regain their ability to depolarize. Naltrexone antagonizes κ- and δ-opioid receptors through similar mechanisms. In particular, κ receptor antagonism can relieve its inhibitory effect on the dopamine system, while δ receptor antagonism mainly terminates its associated Gi/o signaling pathway.
Reference(s):
1. Schmitz JM et al. (2001). Naltrexone and relapse prevention treatment for cocaine-dependent patients. Addict Behav.
2. Krystal JH et al. (2008). Naltrexone is associated with reduced drinking by alcohol dependent patients receiving antidepressants for mood and anxiety symptoms: results from VA Cooperative Study No. 425, "Naltrexone in the treatment of alcoholism". Alcohol Clin Exp Res.
3. Ray LA et al. (2010). Naltrexone for the treatment of alcoholism: clinical findings, mechanisms of action, and pharmacogenetics. CNS Neurol Disord Drug Targets.