Table 2.
Potencies and efficacies of ligand agonism and inactivation of human α4β2-, α6/3β2β3-, and α3β4*-nAChRs1.
| Compound | LF-3-88 | Nicotine | Varenicline | |
|---|---|---|---|---|
| Agonism α4β2-nAChR | EC50 (nmol/L) | 43 | 295 | 938 |
| pEC50 | 7.37 ± 0.19 | 6.53 ± 0.05 | 6.03 ± 0.15 | |
| HS Efficacy (%) | 69 ± 5.6 | 124 ± 8.5 | 105 ± 4.4 | |
| LS Efficacy (%) | −7.8 ± 3.8 | 70 ± 5.9 | 34 ± 2.8 | |
| Inactivation α4β2-nAChR | IC50 (nmol/L) | 32 | 427 | 32 |
| pIC50 | 7.50 ± 0.26 | 6.37 ± 0.06 | 7.50 ± 0.26 | |
| Efficacy (%) | 68 ± 4.9 | 92 ± 2.1 | 79 ± 3.3 | |
| Agonism (α6/3)β2β3-nAChR | EC50 (nmol/L) | 22.4 | 127 | 18 |
| pEC50 | 7.65 ± 0.06 | 6.9 ± 0.03 | 7.75 ± 0.07 | |
| Efficacy | 10 ± 0.27 | 56 ± 0.06 | 17 ± 0.5 | |
| Inactivation (α6/3)β2β3-nAChR | IC50 (nmol/L) | 192 | 85 | 68 |
| pIC50 | 6.72 ± 0.07 | 7.07 ± 0.08 | 7.17 ± 0.08 | |
| Efficacy (%) | 74 ± 2.8 | 26 ± 1.4 | 74 ± 2.6 | |
| Agonism α3β4*-nAChR | EC50 (nmol/L) | ND | 30000 | 2200 |
| Efficacy (%) | ND | 90 | 110 | |
nAChR, nicotinic acetylcholine receptor.
1
See Materials and Methods for details. The term “inactivation” is used because the compounds may be acting to desensitize receptors or as competitive or noncompetitive antagonists, and further work is needed to make such a distinction.