Table 1.
Binding Affinities of Compounds 3–5 at Seven Rat nAChR Subtypes
| Compd. | Ki (nM)a | LogBBd | ||||||
|---|---|---|---|---|---|---|---|---|
| α2β2 | α2β4 | α3β2 | α3β4 | α4β2 | α4β4 | α4β2*b | ||
| 3 | 0.90±0.05 | 1410e | 16±4 | >10,000 | 0.67±0.20 | 182 | 1.9±0.3 | −0.93 |
| 4 | 0.32±0.04 | 310 | 2.9±0.5 | 6660 | 0.31±0.10 | 81±7 | 0.61±0.10 | −0.99 |
| 5 | 0.76±0.20 | 518 | 8.4±1.5 | >10,000 | 0.37±0.10 | 219 | 1.8±0.2 | −0.99 |
| Nicotinec | 5.5 | 70 | 29 | 260 | 4.9 | 23 | 9.8 | 0.03 |
a
See Experimental Section.
b
The asterisk means that other unidentified subunits also may be present, because membrane fractions prepared from rat forebrain contain nAChR subtypes whose subunit composition has not been precisely determined, although they have features of nAChRs containing α4 and β2 subunits.
c
The binding data for nicotine are from the PDSP Assay Protocol Book (http://pdsp.med.unc.edu/).
d
LogBB was calculated using the following equation: LogBB = −0.0148PSA + 0.152CLogP + 0.139.
e
SEM values are not provided for Ki values >100 nM.