Table 2.
[35S]GTPγS Functional Assays in Transfected Cell Lines
| compd | [35S]GTPγS functional assaysa
|
|||||
|---|---|---|---|---|---|---|
| MOR-1
|
KOR-1
|
DOR-1
|
||||
| EC50 (nM) | Emax (%) | EC50 (nM) | IC50 (nM) | EC50 (nM) | IC50 (nM) | |
| 1 | 203 ± 13 | 65 ± 2.8 | – | >4 μM | – | >4 μM |
| 2 | 53 ± 4 | 77 ± 5 | – | 2524 ± 552 | – | 691 ± 434 |
| 3 | 1.7 ± 0.1 | 84 ± 5 | – | 31 ± 3 | – | 61 ± 6 |
| 4 | 2.0 ± 0.1 | 124 ± 2 | – | – | – | 293 ± 129 |
| 6 | 1.4 ± 0.03 | 116 ± 2 | – | 252 ± 48 | – | 193 ± 48 |
| 7 | 0.7 ± 0.2 | 122 ± 2 | – | 721 ± 58 | – | 73 ± 3 |
| 8 | 1.4 ± 0.25 | 123 ± 5 | – | 171 ± 10 | 0.83 ± 0.37 (89 ± 3)b | – |
| 9 | 1.5 ± 0.3 | 100 ± 1 | – | 202 ± 14 | – | 39 ± 5 |
| 10 | 3.9 ± 0.5 | 120 ± 6 | – | – | – | – |
| 11 | – | – | – | – | – | – |
| 12 | – | – | – | – | – | – |
| DAMGO | 19 ± 7 | – | – | – | – | – |
| U50,488H | – | – | 17 ± 6.1 | – | – | – |
| DPDPE | – | – | – | – | 10 ± 2.2 | – |
| NTI | – | – | – | – | – | 0.72 ± 0.11 |
| norBNI | – | – | – | 2.9 ± 0.14 | – | – |
a
Efficacyata were obtained using agonist induced stimulation of [35S]GTPγS binding assay. Efficacy is represented as EC50 (nM) and percent maximal stimulation (Emax) relative to standard agonist DAMGO (MOR-1), DPDPE (DOR-1), or U50,488H (KOR-1) at 1000 nM. To determine the antagonist properties of a compound, membranes were incubated with 100 nM of the appropriate agonist in the presence of varying concentrations of the compound
b
Compound 8 is an agonist at DOR-1. Results are presented as nM ± SEM from three independent experiments performed in triplicate. “–” Denotes not determined or not applicable.