Table 1.
Comparison of Inhibition of Agonist-Stimulated [35S]GTPγS Binding in Cloned Human μ, δ, and κ Opioid Receptors for 6, 7a,b, 8a,b, 9a,b, and 10a,b to 3 and 1a,b
| compd | μ, DAMGO Ke (nM) |
δ, DPDPE Ke (nM) |
κ, U69,593 Ke (nM) |
μ/κ | δ/κ |
|---|---|---|---|---|---|
| 1 | 26.7 ± 7c | 29 ± 8c | 0.05 ± 0.02c | 520 | 580 |
| 3 | 25.1 ± 3.5c | 76.4 ± 2.7c | 0.02 ± 0.01c | 1255 | 3830 |
| 6 | 2.53 ± 0.34 | 219 ± 41 | 3.93 ± 1.2 | 0.7 | 56 |
| 7a | 6.67 ± 1.2 | 44.8 ± 7.7 | 0.18 ± 0.03 | 37 | 248 |
| 7b | 11.2 ± 2.4 | 205 ± 59 | 1.37 ± 0.36 | 8.2 | 150 |
| 8a | 7.4 ± 2.6 | 197 ± 64 | 0.71 ± 0.16 | 10 | 278 |
| 8b | 5.2 ± 1.6 | 134 ± 26 | 5.7 ± 1.6 | 0.9 | 24 |
| 9a | 5.57 ± 1.27 | 395 ± 122 | 0.99 ± 0.25 | 6 | 399 |
| 9b | 13.4 ± 2.9 | 182 ± 48 | 1.58 ± 0.07 | 8.5 | 115 |
| 10a | 7.9 ± 2.2 | 208 ± 55 | 2.7 ± 2.2 | 2.9 | 77 |
| 10b | 1.8 ± 0.3 | 61 ± 11 | 0.55 ± 0.12 | 3.3 | 111 |
a
Data represent means ± SE from at least three independent experiments.
b
The average percent stimulation and agonist EC50 values for the μ, κ, and δ [35S]GTPγS binding assays were 200% and 120 nM, 220% and 380 nM, and 50% and 6 nM, respectively. Ke values were calculated from experiments were the antagonist produced at least a 4-fold shift in the agonist ED50.
c
The Ke values for 3 supplied by the NIDA Opioid Treatment Discovery Program (OTDP) were 3.41, 79.3, and 0.01 nM for the μ, δ, and κ receptors, respectively (ref. 24).