TABLE 4.
Affinity of nAChR compounds for various nAChR subtypes. Autoradiography was used to measure the Ki of the nAChR drugs for α4β2* and α6β2* nAChRs (columns 2 and 3) using control rat striatal sections. 125I-Epibatidine binding in the presence of the α6β2* nicotinic receptor antagonist α-CtxMII was used to identify α4β2*, while 125I-α-CtxMII was used to detect α6β2* nAChRs. Compounds were tested at concentrations ranging from 10−14 to 10−6 M, depending on the specific compound. Each value represents the mean ± SEM of 8 to 10 rats. To determine the interaction of nAChR compounds at α7, α3β4 and muscle nAChRs membrane binding studies were done (columns 4, 5 and 6). Membranes were prepared from SH-SY5Y cells (α7 nAChRs), TE671 cells (muscle nAChRs) or CHO cells expressing either human α3β4 nAChRs or human α7 nAChRs. Binding to the different nAChR subtypes was done as described in Materials and Methods. Binding data are expressed as percent total specific binding, with replicates for each point averaged and plotted against the log concentration of the compound. The values represent an average ± SEM of a seven-point concentration-response curve run in multiple assays.
| Compound | Ki α4β2* nAChRs (nM) | Ki α6β2* nAChRs (nM) | Kiα7 nAChRs (nM) | Ki α3β4 nAChRs (nM) | Ki Muscle(nM) |
|---|---|---|---|---|---|
| TC-2696 | 5.32 ± 0.23 | 6.54 ± 0.62 | 85,000 ± 14682 | 14,000 ± 5046 | > 100,000 |
| TI-10165 | 30.2 ± 0.8 | 8.60 ± 0.90 | 15,000 ± 5170 | 620 ± 153 | 36,000 ± 15612 |
| TC-8831 | 1.36 ± 0.01 | 0.29 ± 0.03 | 620 ± 95 | 270 ± 63 | 470 ± 86 |
| TC-10600 | 17.4 ± 3.40 | 51.8 ± 2.40 | 790 ± 73 | 1,100 ± 159 | 7,100 ± 1641 |
| Sazetidine | 0.78 ± 0.34 | 0.05 ± 0.01 | 3,300 ± 745 | 30 ± 2 | 180 ± 84 |
| Nicotine | 3.10 ± 0.16 | 1.56 ± 0.09 | 2,800 ± 438 | 350 ± 101 | 3,500 ± 2637 |
| Varenicline | 0.31 ± 0.03 | 0.08 ± 0.01 | 290 ± 34 | 160 ± 84 | 160,000 ± 9206 |