Table 1. Binding and Efficacy Results for 1 and Analoguesa.
|
Ki (nM) |
|||||||||
|---|---|---|---|---|---|---|---|---|---|
| sequence | MOPr | DOPr | KOPr | efficacy (% of control), MOPr | EC50 (nM), MOPr | efficacy (% of control), DOPr | Ke (nM), DOPr | efficacy (% of control), KOPr | |
| 1b | Dmt-c(SEtS)[DCys-Aci-DPen]OH | 2.4 ± 0.7 | 2.3 ± 0.5 | 776 ± 149 | 59 ± 11 | 4.7 ± 0.7 | dns | 4.4 ± 1.4 | dns |
| 2 | Dmt-c(SEtS)[DCys-Aic-DPen]SerOH | 10.3 ± 2.3 | 4.5 ± 1.0 | 7100 ± 1260 | 61.4 ± 8.7 | 35.0 ± 12 | dns | dns | |
| 3 | Dmt-c(SEtS)[DCys-Aic-DPen]SerNH2 | 0.53 ± 0.07 | 0.93 ± 0.11 | 93.4 ± 1.4 | 17.3 ± 1.2 | 3.4 ± 1.0 | dns | dns | |
| 4 | Dmt-c(SEtS)[DCys-Aic-DPen]Ser(Glc)NH2 | 1.74 ± 0.2 | 2.43 ± 0.34 | 420 ± 25 | 41.3 ± 2.8 | 36.9 ± 8.4 | dns | 6.1 ± 1.5 | dns |
a
Binding affinities (Ki) were obtained by competitive displacement of radiolabeled [3H]diprenorphine. Efficacy data were obtained using [35S]GTPγS binding assay. Efficacy is presented as percent maximal stimulation relative to standard agonists DAMGO (MOPr), DPDPE (DOPr), and U69,593 (KOPr) at 10 μM. DOPr equilibrium dissociation constant, Ke, was determined to confirm the antagonist activity of 1 and 4. All values are expressed as the mean ± SEM of three separate assays performed in duplicate. dns = does not stimulate.
b
From ref (14).