Effects of BMS-986187 on ligand affinity and [35S]GTPγS binding at μ, δ, κ, and NOP receptors
| Ki (nM) | Potency (GTPγ35S) (nM) | Emax (GTPγ35S) (% Standard) | ||||
|---|---|---|---|---|---|---|
| Control | BMS-986187 | Control | BMS-986187 | Control | BMS-986187 | |
| µ-ORa | ||||||
| DAMGO | 724 (562–912) | 63 (13–316)f | 91 (55–154) | 16 (6–38)f | 111 (103–119) | 110 (105–115) |
| Methadone | 603 (288–1259) | 25 (19–32)f | 203 (121–284) | 10 (3–24)f | 105 (98–111) | 107 (102–111) |
| Morphine | 229 (178–302) | 71 (43–120)f | 120 (85–166) | 38 (10–151) | 70 (67–74) | 90 (83–97)f |
| δ-ORb | ||||||
| Leu-enkephalin | 221 (119–324) | 7 (3–12)f | 28 (18–42) | 3.6 (1.6–8.2)f | 87 (79–95) | 94 (89–100) |
| SNC80 | 71 (20–122) | 5 (3–7)f | NT | NT | NT | NT |
| TAN67 | 10 (7–14) | 3 (0.2–5.8)f | NT | NT | NT | NT |
| κ-ORc | ||||||
| U69,593d | 0.9 (0.3–1.6) | 0.3 (0.2–0.5)g | 881 (480–1601) | 64 (35–121)f | 105 (82–128) | 104 (89–118) |
| Dynorphin A | NT | NT | 15 (11–19) | 1.0 (0.5–2)f | 100 (95–105) | 95 (86–104) |
| Salvinorin A | NT | NT | 322 (221–471) | 25.9 (11–60)f | 110 (97–122) | 116 (101–131) |
| Diprenorphine | NT | NT | 46 (25–37) | 8.9 (1.9–26) | 31 (25–37) | 56 (47–67)f |
| NOPRe | ||||||
| Nociceptin | NT | NT | 2.6 (2.0–4) | 2.1 (1.5–3) | 102 (94–110) | 105 (100–111) |
| Ro-64-6198 | NT | NT | 13 (8.0–19) | 18 (7.8–45) | 109 (102–115) | 108 (93–123) |
NT, not tested. Values in parentheses represent 95% confidence intervals.
a In C6 rat glioma cells expressing rat μ-OR.
↵b Data taken from Burford et al. (2015).
↵c In CHO cells expressing human κ-OR.
↵d Ki values determined by saturation binding in Tris-buffer.
↵e HEK293 cells expressing human NOPR.
↵f Significantly different from control conditions (nonoverlapping confidence intervals).
↵g P = 0.03 compared with control (paired t test).