Table 3.

log RA_i−G, log RA_i−b, log (RA_i−G/RA_i−b), bias factors to G protein signaling and probability values of KOR agonists. The parameters were calculated from the same agonist concentration-response curves that were used to calculate EC₅₀ and E_max values (Figure 3, Table 2) using the method described by Ehlert and colleagues^25–27. The prototypic selective KOR agonist U50,488H was designated as the “balanced” or standard reference ligand. The bias factor to G protein signaling for a given ligand is defined as the ratio of RA_i−G divided by RA_i−b. Mean ± SEM (n = 3).

	Log RAi-G	Log RAi-b	$\text{Log}\frac{{\text{RA}}_{\text{i-g}}}{{\text{RA}}_{\text{i-b}}}$	G Biased factor (95% CI)	(p value)*
U50,488H	0	0	0	1
Nalfurafine	0.94±0.14	0.28±0.02	0.65±0.40	4.49 (1.79–11.1)	0.010
42B	0.17±0.06	−0.28±0.03	0.46±0.20	2.85 (1.82–4.48)	0.003

G, G proteins; b, β-arrestin; CI: confidence interval.

^*compared to bias factor of 1 by t test.