Compound | NK1R pA2a | h NK1R Ki (nM)b | MOR EC50 (nM)c, d | DOR EC50 (nM)c, d | MOR Ki (nM)e, f | DOR Ki (nM)e, f | KOR
K
i
(nM)
e, f
|
---|
BVD02
| / | / | 0.079 ± 0.0065c | 4400 ± 500c | 60 ± 3e | 130 ± 5e | > 106 e |
BVD03
| / | / | 0.00174 ± 0.00034c | 0.016 ± 0.009c | 15 ± 2e | 5 ± 3e | > 106 e |
AN81
|
/
|
/
| 0.32 ± 0.04d | 0.42 ± 0.02d | 0.15 ± 0.02f | 0.60 ± 0.07f | 118 ± 12f |
SBCHM01
| 7.8 | 0.5 ± 0.1 | 8.51 ± 0.62d | 43.3 ± 6.3d | 0.416 ± 0.012f | 10.4 ± 0.6f | 445 ± 81f |
- a The pA2 value was calculated using the Schild's equation [47]. b Inhibitory constants (Ki) of NK1 receptor ligands, measured for the receptor prototype [3H]-SP in the presence of hNK1-CHO membranes. Results are means ± SEM of three independent experiments. Binding data were calculated using the nonlinear regression/one site competition fitting options of the GraphPad Prism Software. c Agonist properties of peptides on forskolin-stimulated cAMP accumulation by MOR and DOR [31, 48]. d Values represent means of 3-6 experiments ± SEM in the GPI (functional assay is representative of MOR activation) and MVD (DOR-representative assay) tissue bioassays [32, 49]. e Binding affinities of compounds for MOR and DOR were determined by displacing [3H]diprenorphine in HEK293 cells stably expressing MOR, DOR and KOR [31]. f Displacement of [3H]DAMGO and [3H]DSLET, respectively, from rat brain membrane binding sites and binding affinities for κ opioid receptors were measured by displacement of [3H]U69,593 from guinea pig brain membrane binding sites [32].