. 2020 Mar 27;10:5653. doi: 10.1038/s41598-020-62530-w

Table 2.

Comparison of Functional Activities at Opioid Receptors of N-Methylmorphinans 1–4 and Their N-Phenethyl Analogues 1a–4a.

Compound	µORa		δORa		κORa
Compound	EC₅₀ (nM)	% stim.	EC₅₀ (nM)	% stim.	EC₅₀ (nM)	% stim.
Morphine (1)	34.4 ± 5.1^b	89 ± 17^b	668 ± 65^b	109 ± 14^b	710 ± 23^b	76 ± 2^b
1a	10.3 ± 0.9^b*	113 ± 8^b	712 ± 86^b	138 ± 17^b	1049 ± 29^b	19 ± 2^b***
Oxymorphone (2)	7.80 ± 1.61^b	92 ± 5^b	259 ± 33^b	87 ± 40^b	463 ± 116^b	48 ± 11^b
2a	2.67 ± 1.06^b*	97 ± 3^b	131 ± 60^b	101 ± 9^b	225 ± 74^b	7.5 ± 0.01^b*
14-OMO (3)	1.21 ± 0.48	95 ± 5	38.5 ± 6.9	102 ± 4	135 ± 29	65.9 ± 6.5
3a	1.26 ± 0.63	98 ± 10	9.34 ± 0.60*	107 ± 5	144 ± 9	35.4 ± 7.5*
14-MM (4)	2.66 ± 0.58	99 ± 5	36.8 ± 12.4	100 ± 9	181 ± 9	68.9 ± 9.2
4a	1.86 ± 0.84	102 ± 13	9.54 ± 2.33*	103 ± 2	334 ± 114	51.3 ± 10.4

^aDetermined in [³⁵S]GTPγS binding assays using membranes from CHO cells stably expressing the human opioid receptors. Percentage stimulation (% stim.) relative to the agonist DAMGO (µOR), DPDPE (δOR) or U69,593 (κOR). Values represent the mean ± SEM (n = 3–4). ^bData from ref. ¹³. *P < 0.05, **P < 0.01 and ***P < 0.001 for N-methylmorphinans vs. respective N-phenethyl analogues (unpaired t-test).