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Table 1 In vitro functional activities and affinities of opioid- and opioid-NK1 ligands

From: In vivo antinociception of potent mu opioid agonist tetrapeptide analogues and comparison with a compact opioid agonist - neurokinin 1 receptor antagonist chimera

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
  1. 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].