Table 2.
Compound | α7-nAChRa | Heteromeric nAChR subtypes b | 5-HT3 c | Selectivity | ||||||
---|---|---|---|---|---|---|---|---|---|---|
α2β2 | α2β4 | α3β2 | α3β4 | α4β2 | α4β4 | α7/α4β2 | α7/5HT3 | |||
7a | 0.37, 0.45 | >10000 | 4000 | 1000 | 709 | 562 | 1000 | 230 | 1370 | 561 |
7b | 1.02, 1.37 | ntd | nt | nt | nt | nt | nt | nt | - | - |
7c | 1.32, 1.35 | 1000 | 8000 | 2000 | 5000 | 885 | 3000 | 505 | 663 | 378 |
7d | 1.83, 2.45 | 292 | 838 | 678 | 3000 | 141 | 1000 | nt | 66 | - |
7e | 17.8, 20.3 | >10000 | 562 | 2000 | 261 | 4000 | 251 | nt | 210 | - |
10 | 0.34, 0.35 | nt | nt | nt | nt | nt | nt | nt | - | - |
11 | 3.41, 6.21 | nt | nt | nt | nt | nt | nt | nt | - | - |
14 | 0.93, 1.93 | nt | nt | nt | nt | nt | nt | nt | - | - |
15 | 6.46, 8.77 | 784 | 6000 | 1000 | 9000 | 477 | 5000 | nt | 63 | - |
Rat cortical membranes, radiotracer [125I]α-bungarotoxin (0.1 nM), KD = 0.7 nM
Inhibition in vitro binding assay of all heteromeric nAChR subtypes was performed with stably transfected HEK293 cells and [3H]epibatidine (0.5 nM), KD = 0.021 nM (α2β2-nAChR), KD = 0.084 nM (α2β4-nAChR), KD = 0.034 nM (α3β2-nAChR), KD = 0.29 nM (α3β4-nAChR), KD = 0.046 nM (α4β2-nAChR), KD = 0.094 nM (α4β4-nAChR).55
Human 5-HT3 recombinant/HEK293 cells, radiotracer [3H]GR65630 (0.35 nM), KD = 0.5 nM
nt = not tested