Naltrexone is a narcotic antagonist used in opioid overdose.. It is also used to treat alcohol dependence in conjunction with behavioural programs. Naltrexone inhibits Mu, Kappa, and Delta opioid receptors, with the highest affinity for the mu-type opioid receptors. This inhibits the exchange of GTP for GDP which is required to activate the G-protein complex. This prevents the Gi subunit of the mu opioid receptor from inhibiting adenylate cyclase, which can therefore continue to catalyze ATP into cAMP. cAMP increases the excitability in spinal cord pain transmission neurons which allows the patient to feel pain rather than the analgesic effects of opioids. The inhibition of Mu-type opioid receptors also prevents the Gi subunit of the mu opioid receptor from activating the inwardly rectifying potassium channel increasing K+ conductance which would cause hyperpolarization. Naltrexone also prevents the gamma subunit of the mu opioid receptor from inhibiting the N-type calcium channels on the neuron. This allows calcium to enter the neuron and depolarize. The inhibition of mu-opioid receptors prevents hyperpolarization in the neuron, allowing it to fire at a normal rate. The neuron is able to depolarize and the high concentration of calcium releases GABA into the synapse which binds to GABA receptors. GABA receptors inhibits dopamine cell firing in the pain transmission neurons. This prevents the analgesic and depressive effects of opioids, preventing opioid overdose. GABA also inhibits dopamine cell firing in the reward pathway which is the main cause of addiction to opioids and other drugs. The major metabolite, 6-β-naltrexol is also a opioid antagonist that may contribute to the effects of naltrexone.

Naltrexone Opioid Antagonist Pathway References