Table 2.
Binding Affinities of Bifunctional Peptides at δ/μ Opioid Receptors and NK1 Receptors
| hDOR,a [3H]DPDPE |
rMOR,b [3H]DAMGO |
rNK1,c [3H]substance P |
|||||
|---|---|---|---|---|---|---|---|
| no. | log IC50f | Ki (nM) | log IC50f | Ki (nM) | Ki(μ)/Ki(δ) | log IC50f | Ki (nM) |
| 1 | −7.50 ± 0.14 | 15 | −7.22 ± 0.10 | 28 | 1.9 | −8.53 ± 0.07 | 0.88 |
| 2 | −6.70 ± 0.13 | 93 | −6.09 ± 0.15 | 380 | 4.1 | −8.00 ± 0.10 | 3.0 |
| 3 | −7.11 ± 0.06 | 36 | −7.24 ± 0.15 | 27 | 0.75 | −8.47 ± 0.02 | 1.0 |
| 4 | −7.97 ± 0.07 | 5.0 | −7.30 ± 0.07 | 23 | 4.7 | −8.57 ± 0.13 | 0.80 |
| 5 | −8.22 ± 0.06 | 2.8 | −7.11 ± 0.11 | 36 | 13 | −9.02 ± 0.10 | 0.29 |
| 6 | −7.92 ± 0.04 | 4.8 | −7.89 ± 0.07 | 5.5 | 1.1 | −9.11 ± 0.02 | 0.20 |
| 7 | −8.42 ± 0.15 | 1.8 | −7.69 ± 0.05 | 9.7 | 5.4 | −8.69 ± 0.19 | 0.60 |
| 8 | −6.79 ± 0.13 | 77 | −6.54 ± 0.09 | 140 | 1.8 | −8.54 ± 0.03 | 0.71 |
| biphalind | — | 2.6 | — | 1.4 | — | — | — |
| DADLEe | — | 1.3 | — | 15 | — | — | — |
| L-732,138 | −6.40 ± 0.03 | 134 | |||||
Radioligand competition analysis for the hDOR was carried out using [3H]DPDPE (Kd = 0.50 ± 0.1 nM).
Radioligand competition analysis for the rMOR was carried out using [3H]DAMGO (Kd = 0.85 ± 0.2 nM).
Radioligand competition analysis for the rat NK1 receptor was carried out using [3H] substance P (Kd = 0.16 ± 0.03 nM). The log IC50 ± standard error are expressed as logarithmic values determined from the nonlinear regression analysis of data collected from two independent experiments (four independent experimental values per drug concentration). The Ki values are calculated using the Cheng and Prusoff equation to correct for the concentration of the radioligand used in the assay.
Reference 52.