Table 2.

Salvinorin A is a potent κ-opioid agonist: [³⁵S]GTP-γ-S studies using guinea pig brain caudate membranes

Drug	Unblocked	CTAP, 200 nM	TIPP, 20 nM	Nor-BNI, 0.2 nM
Percent stimulation
DAMGO	414  ± 47	11,124  ± 2,126	494  ± 56	355  ± 61
	0.96  ± 0.02	0.99  ± 0.09	0.97  ± 0.02	0.92  ± 0.03
SNC80	758  ± 131	987  ± 120	9,565  ± 4,115	855  ± 119
	0.91  ± 0.04	0.94  ± 0.03	0.90  ± 0.19	0.86  ± 0.3
U69,593	377  ± 39	540  ± 57	442  ± 76	1,554  ± 168
	1.70  ± 0.04	1.70  ± 0.04	1.60  ± 0.06	1.60  ± 0.05
Percent of maximal stimulation produced by 10 μM U69,593
Salvinorin A	235  ± 26	204  ± 20	259  ± 40	643  ± 128
	0.79  ± 0.04	0.83  ± 0.03	0.81  ± 0.06	0.89  ± 0.10

[³⁵S]-GTP-γ-S-binding assays were conducted as described in Materials and Methods. Agonist dose–response curves were generated by using 8–10 drug concentrations in the absence and presence of fixed concentrations of selective antagonists: CTAP to block μ receptors, TIPP to block δ receptors, and nor-BNI to block κ receptors. The concentrations were chosen on the basis of previous studies to selectively block the targeted receptor. Values in parentheses are the maximal percent stimulation. For Salvinorin-A, the value is reported as a percent of the stimulation produced by 10 μM U69,593. Each value is ± SD (n = 3). DAMGO, [d-Ala-2-MePhe⁴,Gly-ol⁵]enkephalin; CTAP, d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH₂; TIPP, H-Tyr-Tic-Phe-Phe-OH.