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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].