Table 2. Pharmacological evaluation analogues 1e and 6j-u, tested at 10 μM against an ACh-mediated concentration-response curve.
Compound # | R1 | Δbaselinea | ΔpEC50 | ΔEmaxb |
---|---|---|---|---|
1e | 103.2 ± 2.85 | 1.48 ± 0.20 | 44.7 ± 2.74 | |
6j | 32.1 ± 2.52* | 1.15 ± 0.10 | 21.8 ± 2.97* | |
6k | 51.4 ± 9.53* | 0.76 ± 0.26* | 128.8 ± 9.68 | |
6l | 8.48 ± 4.01* | 1.27 ± 0.15 | 5.60 ± 4.45* | |
6m | 88.1 ± 4.09 | 1.31 ± 0.17 | 80.6 ± 4.78* | |
6n | 51.7 ± 4.21* | 1.35 ± 0.17 | 53.5 ± 5.54 | |
6o | 33.2 ± 4.25* | 0.25 ± 0.11* | 97.7 ± 4.47* | |
6p | 78.2 ± 5.58* | 1.99 ± 0.19 | 61.3 ± 3.81 | |
6q | 77.3 ± 3.17* | 1.33 ± 0.13 | 65.6 ± 3.48* | |
6r | 52.2 ± 5.62* | 1.63 ± 0.17 | 57.7 ± 4.85 | |
6s | 89.7 ± 6.11 | 2.57 ± 0.25* | 73.3 ± 7.00* | |
6t | 83.3 ± 4.16* | 2.11 ± 0.18* | 50.5 ± 3.60 | |
6u | 18.6 ± 3.70* | 1.24 ± 0.11 | 39.0 ± 3.53 |
Data represent the mean ± SEM of 4 independent experiments performed in duplicate. Only the change in pEC50, baseline and Emax for the 10 μM concentrations of PAMs are reported, with the full ACh concentration-response curves in the presence of 1 μM and 10 μM PAMs shown in Supp. Fig. 3. Data were analysed by one-way ANOVA and compared to the control PAM, 1e, with a post-hoc Dunnett test
where *p < 0.05 was considered to be significantly different.
Δbaseline is expressed as a percentage of the maximum ACh response in the absence of PAM.
ΔEmax is expressed as a percentage of the maximum ACh response in the absence of PAM.