Table 2.
Comparison of antinociceptive potency of peptidomimetics 1–9 and of reference compounds (enkephalin analog and SHU9119), in acute pain (tail-flick test) and neuropathic pain in CCI-exposed mice (von Frey and cold plate test). The experiments were performed on naive mice or 7–14 days after CCI procedure, and all compounds were administered intraspinally (i.t.). The results are shown as ED50 value with 95% confidence limits (CL) determined on the quantal data.
| Code | Compound | ED50 (CL) [nmol] Naive Mice (Acute Pain) Tail-Flick |
ED50 (CL) [nmol] Mice Subjected to CCI (Neuropathic Pain) |
|
|---|---|---|---|---|
| Von Frey (Allodynia) | Cold Plate (Hyperalgesia) | |||
| 1 | ENK-d-Ala-SHU | # | # | # |
| 2 | ENK-β-Ala-SHU | 58.8 (27–128) | 0.04 (0.03–0.68) | 142 (31–654) |
| 3 | ENK-Ahx-SHU a | # | 0.0002 (0.00005–0.001) | 0.004 (0.005–0.01) |
| 4 | ENK-(Ahx)2-SHU a | * | 0.01 (0.00002–7.8) | 0.1 (0.004–3.4) |
| 5 | ENK-4AMB-SHU | * | 0.02 (0.005–0.5) | 0.16 (0.1–0.2) |
| 6 | ENK-4APhAc-SHU | 42 (21–85) | 0.02 (0.0002–1.03) | 0.02 (0.0005–1.2) |
| 7 | ENK-Pro-Gly-SHU | # | 0.4 (0.3–0.6) | 0.16 (0.07–0.34) |
| 8 | ENK-(Pro-Gly)2-SHU | 5 (0.4–60.3) | * | * |
| 9 | [Dmt1]ENK-Ahx-SHU a | # | 0.003 (0.000003–3.45) | 0.009 (0.005–0.01) |
| Tyr-d-Ala-Gly-Phe-NH2 | 0.05 (0.03–0.09) | 0.3 (0.2–0.4) | 16.3 (4.7–56) | |
| SHU9119 a | * | 3.33 (0.009–7.5) | # | |
*—lack of analgesic effect, # weak analgesic effects, poor dose dependency, ED50 cannot be calculated, a detailed in vivo study was previously presented in [27].