Figure 1.

Model of μ opioid receptor (MOR) conformations. MOR-μ* is reversibly activated by both spontaneous conversion and agonists to ligand-free active MOR-μ*. Opioid agonists appear to dissociate from MOR-μ* by losing high-affinity binding. The inverse agonist naltrexone potently blocks ligand-free MOR-μ*, whereas the neutral antagonist 6BN binds to MOR-μ* but does not suppress signaling. Both naltrexone and 6BN block agonist activation competitively at MOR-μ with lower potency. Continued opioid agonist stimulation shifts the equilibrium to persistent MOR-μ* signaling, leading to a dependent state. In contrast to naltrexone, 6BN is proposed to potently accelerate reversal of the equilibrium back to MOR-μ in the opioid-naïve state. Adapted from [20].