TABLE 3.
Functional properties of α-conotoxin analogues at the human α7 and the rat α3β4 nAChRs
The IC50 values are from Fluo-4/Ca2+ assay at human α7-GH3 and rat α3β4-HEK293 cell lines using EC80-EC90 values of the agonist (30 μm ACh for human α7-GH3 and 300 nm epibatidine for rat α3β4-HEK293). The IC50 values are the means of 3-5 experiments and are given in μm with pIC50 ± S.E. values in parentheses.
| Compounds | α7 | α3β4 |
|---|---|---|
| Reference ligands | ||
| ACh EC50 | 15 (4.82 ± 0.04) | NDa |
| Epibatidine EC50 | ND | 0.071 (7.14 ± 0.04) |
| MLA | 0.0056 (8.25 ± 0.04) | ND |
| ImI Pro6 analogues | ||
| WT | 2.6 (5.58 ± 0.04) | >300 (<3.5) |
| 4-(R)-Hydroxy | ∼100 (∼4) | >300 (<3.5) |
| 4-(R)-Amino | >300 (<3.5) | >300 (<3.5) |
| 4-(S)-Amino | ∼300 (∼3.5) | >300 (<3.5) |
| 4-(R)-Guanidino | >300 (<3.5) | >300 (<3.5) |
| 4-(R)-Betainamidyl | >300 (<3.5) | >300 (<3.5) |
| 4-(R)-Fluoro | 30-100 (4.5-4) | >300 (<3.5) |
| 4-(S)-Fluoro | 30-100 (4.5-4) | >300 (<3.5) |
| 4-(R)-Phenyl | 14 (4.85 ± 0.05) | >300 (<3.5) |
| 4-(S)-Phenyl | >300 (<3.5) | >300 (<3.5) |
| 4-(R)-Benzyl | 30-100 (4.5-4) | >300 (<3.5) |
| 4-(R)-Naphthylmethyl | 30 (4.52 ± 0.05) | 19 (4.71 ± 0.05) |
| 3-(S)-Phenyl | 11 (4.94 ± 0.04) | >300 (<3.5) |
| 5-(R)-Phenyl | 0.70 (6.15 ± 0.04) | 3.7 (5.43 ± 0.05) |
| PnIA[A10L] Pro6 analogues | ||
| WT | 0.51 (6.18 ± 0.02) | >300 (<3.5) |
| 4-(R)-Hydroxy | ∼300 (∼3.5) | >300 (<3.5) |
| 4-(R)-Amino | >300 (<3.5) | >300 (<3.5) |
| 4-(S)-Amino | ∼300 (∼3.5) | >300 (<3.5) |
| 4-(R)-Guanidino | >300 (<3.5) | >300 (<3.5) |
| 4-(R)-Betainamidyl | ∼300 (∼3.5) | >300 (<3.5) |
| 4-(R)-Fluoro | ∼100 (∼4) | >300 (<3.5) |
| 4-(S)-Fluoro | 30-100 (4.5-4) | >300 (<3.5) |
| 4-(R)-Phenyl | 26 (4.5 ± 0.05) | >300 (<3.5) |
| 4-(S)-Phenyl | 33 (4.6 ± 0.04) | >300 (<3.5) |
| 4-(R)-Benzyl | 30-100 (4.5-4) | ∼100 (∼4) |
| 4-(R)-Naphthylmethyl | 30-100 (4.5-4) | ∼100 (∼4) |
| 3-(S)-Phenyl | >300 (<3.5) | >300 (<3.5) |
| 5-(R)-Phenyl | >300 (<3.5) | >300 (<3.5) |
a
ND means not determined.