Table 1. Experimentally determined and predicted binding affinity ranges of the 23 opioids docked at the μOR.

The 8 fentanyl derivatives and 7 fentanyl congeners are listed first and ordered by increasing binding affinity, and the 8 morphine derivatives are listed last. The green labels indicate that the model correctly predicted the binding concentration regime, yellow indicates that the model predicted the compound to bind stronger than the measured K_i, and red indicates that the model predicted the compound to bind less strongly than the measured K_i.

Drug	Human Ki (nM) [35]	Marmoset Ki (nM) [38]	Guinea Pig Ki (nM) [13]	Average Docking Score (ADS)	Standard Deviation in Score	Predicted Conc. Regime
N-methyl fentanyl*			18000 ± 3000	-7.89	0.21	> 100 nM
(1R,2R)Tramadol	12,500			-7.85	0.06	> 100 nM
(1S,2S) Tramadol	12,500			-7.97	0.20	> 100 nM
Meperidine	450			-7.77	0.07	> 100 nM
Propoxyphene	120			-9.56	0.08	0–100 nM
N-Methyl carfentanil*			42 ± 6	-8.53	0.07	0–100 nM
Diphenoxylate	12.4			-10.1	0.47	Sub nM
Alfentanil	7.39	14.4 ± 4.2		-10.5	0.56	Sub nM
R-Methadone	3.38			-8.69	0.12	0–100 nM
S-Methadone	3.38			-8.63	0.07	0–100 nM
Fentanyl	1.35	1.32 ± 0.35	1.2 ± 0.2	-9.43	0.38	0–100 nM
Sufentanil	0.138	0.24 ± 0.05		-9.89	0.23	Sub nM
Carfentanil^		0.22 ± 0.08	0.024 ± 0.004	-10.8	0.30	Sub nM
Lofentanil^		0.055 ± 0.006	0.023 ± 0.004	-10.8	0.50	Sub nM
R30490*			0.09 ± 0.01	-10.3	0.31	Sub nM
Codeine	734			-8.23	0.16	> 100 nM
(+)-Pentazocine	118			-7.77	0.12	> 100 nM
Oxycodone	25.9			-8.78	0.27	0–100 nM
Nalbuphine	2.12			-8.47	0.29	0–100 nM
Morphine	1.14			-7.76	0.14	> 100 nM
Oxymorphone	0.406			-8.40	0.18	0–100 nM
Hydromorphone	0.365			-7.94	0.26	> 100 nM
Buprenorphine	0.216			-9.76	0.48	0–100 nM

*Experimental data from guinea pig whole brain membranes.

^Experimental data from marmoset brain homogenates.