Table 1. In vitro activities of 12-epi-salvinorin A and its analogues.

Compound	R1	R2	R3	hKOPR binding Ki± SEMa,b (nM)	rMOPR binding Ki± SEMb,c (nM)	hKOPR [35S]GTPγS		hKOPR β-arrestin 2
						EC50 ± SEMb,d (nM)	Emax ± SEMe	EC50f (nM)	Emaxg
1, 12-epi-salvA	Ac	H	H	41 ± 5h	_h,i	41 ± 6	73 ± 6	382 ±85	126 ± 10
2		H	H	4.4 ± 0.4	_i	_j	∼100%k	_j	_j
3		H	H	2.5 ± 0.3	_i	9.5 ± 1.2	103 ± 3	123 ±38	127 ±9
4	H	H	H	63 ±5	_i	_j	∼100%k	_j	_j
5	Ac	Br	H	18 ± 1	_i	_j	∼100%k	_j	_j
6	Ac	Br	Br	40 ± 1	318 ±39	_j	∼100%k	_j	_j
SalvA				3.0 ± 0.1	_i	6.9 ± 0.5	98±3	31 ± 14	100
U50,488H				4.5 ± 0.2	_i	5.7 ± 0.5	100	_j	_j
Nalbuphine				_j	_j	65 ± 10	61 ± 3	250 ±152	13 ±9

^aK_i values in inhibiting [³H]diprenorphine binding to human KOPR (hKOPR).

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

^cK_i values in inhibiting [³H]diprenorphine binding to rat MOPR (rMOPR).

^dEC₅₀ values in activating the hKOPR to enhance [³⁵S]GTPγS binding.

^eEfficacy determined as the % of maximal response ± SEMs produced by U50,488H run in parallel experiments.

^fEC₅₀ values in promoting the hKOPR to couple to β-arrestin 2.

^gEfficacy determined as the % of maximal response ± SEMs produced by salvA run in parallel experiments.

^hData from Ref. 11.

ⁱTest compound at 3 μM inhibited <50% radioligand binding.

^jNot determined.

^kTest compound at 3 μM induced maximum activation of the KOPR.