Table 3.

Effects of Aryl, Carbonyl, and Amino Substitutions on Affinity, Potency, and Efficacy^a

		Binding affinity Ki (nM)			DOR Ki/MOR Ki	Potency, EC50 (nM)			Efficacy, (% stimulation)
Cmpd	R2	MOR	DOR	KOR		MOR	DOR	KOR	MOR	DOR	KOR
7a		1.0 (0.1)	1.6 (0.4)	23 (5)	2	4 (2)	380 (84)	dns	96 (4)	42 (7)	dns
7l		0.37 (0.07)	1.4 (0.7)	27 (8)	4	44 (17)	33 (13)	dns*	78 (1)	15 (2)	dns*
7m		0.20 (0.06)	1.8 (0.4)	25 (4)	9	2.1 (0.3)	dns	dns	56 (5)	dns	dns
7n		1.0 (0.3)	3.7 (0.3)	47 (2)	4	4.9 (0.3)	dns	dns*	71 (3)	dns	dns*
7o		0.32 (0.08)	5.4 (0.5)	29 (5)	17	1.2 (0.7)	dns	dns*	49 (4)	dns	dns*
7p		0.17 (0.03)	3.0 (0.4)	30 (2)	18	3.4 (1.4)	dns	dns	73 (5)	dns	dns
7r		0.47 (0.16)	2.4 (0.4)	210 (6)	5	4.4 (1.7)	dns	dns	67 (3)	dns	dns
7i		0.07 (0.03)	4.4 (1.0)	0.93 (0.18)	63	2.3 (0.2)	27 (2)	100 (33)	93 (2)	31 (4)	30 (6)
7j		0.15 (0.04)	2.3 (0.7)	7.3 (1.4)	15	1.8 (0.4)	180 (47)	dns	96 (2)	29 (5)	dns
7k		0.35 (0.18)	15 (3)	1.9 (0.5)	43	8.2 (3.5)	290 (100)	170 (67)	60 (2)	18 (1)	17 (1)

^aBinding affinities (K_i) were obtained by competitive displacement of radiolabeled [³H]-diprenorphine in membrane preparations. Functional data were obtained using agonist induced stimulation of [³⁵S]-GTPγS binding assay. Potency is represented as EC₅₀ (nM) and efficacy as percent maximal stimulation relative to standard agonist DAMGO (MOR), DPDPE (DOR), or U69,593 (KOR) at 10 μM. All values are expressed as the mean of three separate assays (n = 3) performed in duplicate unless noted otherwise, with SEM in parentheses.

Asterisk (*) indicates n = 2; dns = does not stimulate (<10% stimulation).