G protein–independent arrestin recruitment was determined in the GPCR Tango assay, as outlined in the Methods. Both W-15 and W-18 were tested and showed no agonist activity at DOR (A), KOR (B), MOR (C), and NOP (D) receptors and no antagonist effect at DOR (E), KOR (F), or MOR (G) receptors. Normalized results represent mean ± SEM of 3 independent experiments, each performed in triplicate (0% for vehicle activity, and 100% for reference activity), and were analyzed in Prism.