Functional properties of nicotine analogs acting on human α7 receptors expressed in Xenopus oocytes
Peak current and net charge estimates were obtained from each response. Mean estimates ± one sample S.D. of the maximum current response (Imax) and potency (EC50) are given.
| Compound | EC50 (µM) | Imax (% of ACh Response) | |||||
|---|---|---|---|---|---|---|---|
| Peak Current | Net Charge | PC/NC Ratio | Peak Current | Net Charge | PC/NC Ratio | n | |
| Nic (N) | 65.3 ± 20 | 21.2 ± 7.4 | 3.1 | 91.5 ± 10 | 85.4 ± 20 | 1.1 | 7 |
| 1′-MeN | 51.4 ± 11 | 16.7 ± 4.5 | 3.1 | 109 ± 11 | 90.3 ± 9.6 | 1.2 | 5 |
| 1′-EtNorN | 85.2 ± 22 | 30.7 ± 12 | 2.8 | 54.1 ± 15*** | 55.9 ± 10 | 1.0 | 9 |
| 2′-MeN | 9.65 ± 4.0*** | 3.15 ± 0.70*** | 3.1 | 82.4 ± 6.9 | 72.0 ± 7.2 | 1.1 | 5 |
| 3′-Trans-MeN | 46.7 ± 14 | 13.8 ± 8.3 | 3.4 | 115 ± 25 | 64.6 ± 11 | 1.8 | 5 |
| 3′-Cis-MeN | 171 ± 45*,ŧŧŧ | 68.1 ± 42* | 2.5 | 92.5 ± 29 | 62.6 ± 8.5 | 1.5 | 5 |
| 4′-Trans-MeN | 246 ± 58*** | 113 ± 32*** | 2.2 | 16.4 ± 4.6*** | 27.3 ± 4.6*** | 0.60 | 4 |
| 4′-Cis-MeN | 277 ± 32*** | 186 ± 120** | 1.5 | 1.81 ± 0.80*** | 8.08 ± 5.6*** | 0.20 | 4 |
| 5′-Trans-MeN | 134 ± 53* | 39.3 ± 15 | 3.4 | 67.4 ± 13 | 54.8 ± 6.6* | 1.2 | 7 |
| 5′-Cis-MeN | 1010 ± 860***,ŧŧ | 479 ± 110***,ŧŧŧ | 2.1 | 4.42 ± 2.0***,ŧŧŧ | 14.8 ± 7.2***,ŧŧŧ | 0.3 | 4 |
n, the number of oocytes used.
↵* P < 0.05, **P < 0.01, ***P < 0.001, comparison with nicotine. (These P values were obtained from one-way ANOVA of log-transformed data with Dunnett’s multiple comparison post-test.)
ŧP < 0.05, ŧŧP < 0.01, ŧŧŧP < 0.001, comparison of cis- and trans-enantiomers; these P values were obtained from a two-tailed t test and, thus, are not corrected for multiple comparisons. Et, ethyl; Me, methyl; N, nicotine; NorN, nornicotine.