Naloxone

Naloxone is an opioid receptor antagonist and a semisynthetic opioid derivative. Naloxone is a potent μ-opioid receptor antagonist and also antagonizes κ- and δ-opioid receptors, although with lower affinity. After naloxone 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. Naloxone 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.