Table 2.

Evaluation of functional activity of selected N-(3-hydroxyphenyl)-3,8-diazabicyclooctanes at DORs, KORs, and NORs using Eurofins DiscoverX HitHunter^® Assays.

	DOR cAMP			KOR cAMP			NOR cAMP
Compound	pEC₅₀±SEM^a	EC₅₀ (nM)	E_max ± SEM (%)^a	pEC₅₀± SEM^a	EC₅₀ (nM)	E_max ± SEM (%)^a	pEC₅₀± SEM^a	EC₅₀ (nM)	E_max ± SEM (%)^a
Morphine	6.3 ± 0.1	500	74.5 ± 4.7	6.5 ± 0.1	320	84.6 ± 3.8	< 5.0	> 10,000	[13.8 ± 5.8]
Fentanyl	6.8 ± 0.1	160	87.5 ± 1.5	6.1 ± 0.1	790	89.7 ± 3.7	< 5.0	> 10,000	[47.0 ± 8.1]
Buprenorphine	9.1 ± 0.2	0.79	65.5 ± 7.8	8.5 ± 0.1	3.2	66.3 ± 6.7	7.3 ± 0.1	50	74.7 ± 4.8
DADLE	10.4 ± 0.1	0.04	87.1 ± 1.8	N/D	N/D	N/D	N/D	N/D	N/D
U50,488H	N/D	N/D	N/D	9.6 ± 0.1	0.25	99.7 ± 0.9	N/D	N/D	N/D
N/OFQ	< 5.0	> 10,000	0	< 5.0	> 10,000	[74.3 ± 3.6]	10.0 ± 0.1	0.10	100.5 ± 0.3
Atoxifent	8.8 ± 0.1	1.6	69.3 ± 7.7	< 5.0	> 10,000	0	< 5.0	> 10,000	[17.4 ± 1.1]
11	8.8 ± 0.1	1.6	71.1 ± 3.6	< 5.0	> 10,000	0	< 5.0	> 10,000	0
12	8.8 ± 0.1	1.6	71.0 ± 4.7	< 5.0	> 10,000	0	< 5.0	> 10,000	0
13	8.0 ± 0.2	10	81.3 ± 3.0	< 5.0	> 10,000	0	< 5.0	> 10,000	0
16	7.8 ± 0.3	16	34.8 ± 3.0	N/D	N/D	N/D	< 5.0	> 10,000	0
17	8.3 ± 0.2	5.0	58.0 ± 2.8	N/D	N/D	N/D	< 5.0	> 10,000	0
18	6.8 ± 0.1	160	56.2 ± 6.2	N/D	N/D	N/D	7.6 ± 0.5	25	41.9 ± 19.3
19	7.9 ± 0.3	13	71.4 ± 1.8	N/D	N/D	N/D	8.5 ± 0.1	3.2	19.5 ± 3.4

Values are expressed as the mean ± SEM of at least three independent experiments; N/D = Not determined; Data in square brackets are max response observed in the test dose range