Structural Assessment of Agonist Efficacy in the μ-Opioid Receptor: Morphine and Fentanyl Elicit Different Activation Patterns
Adrián Ricarte, James A. R. Dalton, Jesús Giraldo
Abstract
conformational changes. In addition to differences in ligand binding, different intracellular receptor conformational changes are observed as morphine preferentially activates transmembrane (TM) helices: TM3 and TM5, while fentanyl preferentially activates TM6 and TM7. As conformational changes in TM6 and TM7 are widely described as being the most crucial aspect in GPCR activation, this may contribute to the greater efficacy of fentanyl over morphine. These computationally observed functional differences between fentanyl and morphine may provide new avenues for the design of safer but not weaker opioid drugs because it is desirable to increase the safety of medicines without sacrificing their efficacy.