Table 3.

Agonist potencies and efficacies at the human µOR and δOR of N-methylmorphinans 1–4 and their respective N-phenethy analogues 1a–4a in the cAMP accumulation assay.

Compound	µORa		δORa
	EC50 (nM)	% stim.	EC50 (nM)	% stim.
Morphine (1)	13.5 ± 2.83	106 ± 9	374 ± 24	94 ± 18
1a	2.87 ± 0.91*	107 ± 5	315 ± 110	105 ± 8
Oxymorphone (2)	2.48 ± 0.79	109 ± 2	56.9 ± 5.1	87 ± 16
2a	0.59 ± 0.04*	97 ± 6	50.1 ± 16.2	99 ± 18
14-OMO (3)	0.19 ± 0.14	90 ± 8	5.42 ± 0.93	98 ± 3
3a	0.078 ± 0.004	88 ± 12	0.60 ± 0.07**	93 ± 2
14-MM (4)	0.31 ± 0.07	93 ± 5	4.06 ± 0.89	99 ± 8
4a	0.15 ± 0.07	98 ± 12	0.55 ± 0.16*	96 ± 4

^aDetermined in the forskolin-induced cAMP accumulation assay using CHO cells co-expressing the human opioid receptors and the cAMP biosensor GloSensor-22F (CHO-hµOR-p22F or CHO-hδOR-p22F cells). Percentage stimulation (% stim.) relative to the agonist DAMGO (µOR) or DPDPE (δOR). Values represent the mean ± SEM (n = 3–4). *P < 0.05 and **P < 0.01 for N-methylmorphinans vs. respective N-phenethyl analogues (unpaired t-test).