Table 1.

Affinities (K_i), potencies (EC₅₀), and efficacies (E_max) of C12-substituted salvinorins at the KOPR.

Compound	R	Ki, nMa,b	EC50, nMb,c	Emaxd
1, SalvA		2.5 ± 0.6	2.1 ± 0.6	105 ± 4
2e		2.9 ± 0.3	2.4 ± 0.2	108 ± 5
3e		7.1 ± 0.1	4.6 ± 0.1	120 ± 6
6		41 ±5	84 ± 8	67 ± 5
7		55 ± 23	167 ± 35	99 ± 1
9		498 ± 71	330 ± 30	98 ± 2
10		497 ± 13	> 1,000	–
11		555 ± 97	299 ± 13	113 ± 3
13		38 ± 10	101 ± 6	103 ± 1
16		83 ± 28	195± 6	103 ± 3
17		20 ± 2	36 ± 5	111 ± 4
18		154 ± 27	361 ± 25	99 ± 2
19		196 ± 23	508 ± 8	94 ± 2
20		109 ± 12	337 ± 54	94 ± 2
U50,488H		2.2 ± 0.2	2.9 ± 0.2	100

^aK_i values in inhibiting [³H]diprenorphine binding to hKOPR.

^bEach value represents the mean of at least three independent experiments performed in duplicate.

^cEC₅₀ values in activating the hKOPR to enhance [³⁵S]GTPγS binding.

^dEfficacy determined as the % of maximal response produced by U50,488 run in parallel experiments.

^eU50,488H values for these assays: K_i = 1.6 ± 0.6 nM; EC₅₀ = 3.2 ± 0.7 nM.