Table 2.
Affinities of compounds 23-31 and 33 for Rat nAChR Subtypes Defined by Competition for [3H]Epibatidine Binding
| Compd. |
Ki (nM) a
|
||||||
|---|---|---|---|---|---|---|---|
| α2β2 | α2β4 | α3β2 | α3β4 | α4β2 | α4β2* b | α4β4 | |
| 23 | NA | NA | NA | NA | 2176 | NA | NA |
| 24 | 0.5±0.1 | 612 | 17.3±5.3 | NA | 0.4±0.1 | 1.1±0.2 | 161 |
| 25 | 18.1±2.3 | >104 | 2534 | NA | 38.8±7 | 221 | >104 |
| 26 | 0.2 | 129.5 | 21±5.7 | NA | 0.3 | 0.5±0.1 | 584.8 |
| 27 | 167.9 | NA | NA | NA | 49.5±8.9 | 173.7 | NA |
| 28 | 43.8±10.7 | NA | 2094 | NA | 28.5±5.6 | 193.8 | NA |
| 29 | 12.9±1.7 | 9959 | 472.5 | NA | 21.7±6.6 | 86.6±15.3 | 9475 |
| 30 | 0.04 | 50.8±10.5 | 0.8±0.2 | 2074 | 0.05 | 0.2 | 30±4.3 |
| 31 | 6.1±0.6 | NA | 191.5 | NA | 90.9±27 | 40.7±5.3 | NA |
| 33 | 3.5±0.5 | 546.6 | 137.3 | NA | 3.3±1 | 15.7±2.8 | 234.1 |
| 4 c | 0.1 | 236 | 2.4 | NA | 0.1 | 0.3 | 50.2 |
| nicotine d | 5.5 | 70 | 29 | 260 | 4.9 | 9.8 | 23 |
| saz-A e | 0.087 | 210 | 0.38 | 1900 | 0.062 | 0.17 | 52 |
a
See Experimental Section. SEM values are not provided for Ki values > 100 nM.
b
α4β2*, prepared from rat forebrain.
c
Ki values for compound 4 are obtained from Reference 15.
d
Ki values for nicotine are taken from the PDSP Assay Protocol Book (http://pdsp.med.unc.edu/).
e
Ki values for sazetidine-A were obtained from the literature.22
NA: not active, defined as < 50% binding in the primary assay at 10 μM.