Figure 2

Biased agonists targeting cell-specific receptor/effector complexes may prove a valid approach for developing longer acting opioid analgesics. Conformational restrictions within receptor-effector complexes present in cell A make them more sensitive to the effect of regulatory proteins than receptor-effector complexes in cell B. If these differences make analgesic responses mediated by cell A more prone to tolerance than those mediated by cell B, a) agonists that preferentially recognize and activate complexes in cell B are expected to produce longer lasting analgesia than b) an equally efficacious agonist that preferentially stimulates complexes in cell A or c) agonists that do not discriminate among complexes.