Nalmefene

Nalmefene is an opioid receptor antagonist. Nalmefene is characterized by strong μ-opioid receptor antagonism, along with κ- and δ-opioid receptor antagonism, and has a long duration of action. After nalmefene 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. Nalmefene 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.