TABLE 2

Effect of salvinorin A derivatives on KOR binding and inhibition of forskolin-stimulated adenylate cyclase in KOR-293 cells

Shown are the mean values ± S.D. from n = 2-4 separate experiments in which Ki values for inhibition of [3H]bremazocine binding and EC50 and Emax values for inhibition of adenylate cyclase in KOR-293 cells were performed as detailed under Materials and Methods with the response induced by U69593 defined as 100%. The salvinorin A derivatives listed above were also screened at a large number of cloned receptors and found to have no significant activity, when tested at 10 μM at the following receptors: serotonin (5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT5a, 5-HT6, 5-HT7), dopamine (D1, D2, D3, D4, D5), muscarinic (m1, m2, m3, m4, m5), μ, δ, and ORL-1 opioid receptors, σ1, σ2, α1-adrenergic (1a, 1b, 1d), α2-adrenergic (2A, 2B, 2C) β2-adrenergic, and CB-1 cannabinoid receptors [assayed as previously detailed (Shi et al., 2003)].




Ki ± S.E.M. (nM)

EC50 in nM (pEC50 ± S.E.M.)

Emax
Salvinorin A 18.74 ± 3.38 0.63 (−0.2 ± 0.07) 100
Propionate 32.63 ± 15.7 4.7 (0.7 ± 0.3) 100
Heptanoate 3199 ± 961.2 40 (1.6 ± 0.4) 34 ± 11
Privalate >10,000 NA NA
p-Bromobenzoate >10,000 NA NA
2,2,2-Triethylcarbonate >10,000 NA NA
Ethylcarbonate >10,000 NA NA
Piperonylate >10,000 NA NA
1-Napthoate >10,000 NA NA
Cyclopropanecarboxylate >10,000 NA NA
Salvinorin B
>10,000
NA
NA
  • NA not active at 10,000 nM.