Table 2.
Estimates of antagonist potency, derived from isolated guinea pig ileum data, calculated using classical Schild plot, the Gaddum-Schild method, Schild’s equation and antagonist affinity (pKB) determined using the Gaddum method.
| Ligand; receptor |
Slope of Schild plot (+ 95% CI)a |
pA2 Schild plot (+ 95% CI) |
pA2 Gaddum-Schild (+ 95% CI)b |
pA2 Schild’s equation c |
pKB Gaddum |
|
|---|---|---|---|---|---|---|
| NorBNI | ||||||
| κ | 1.46 (0.32 to 2.59) |
8.30 (10.30 to 7.72) |
8.51 (8.00 to 9.02) |
8.20 | 8.75 | |
| 5’-AMN | ||||||
| κ | 1.16 (0.44 to 1.87) |
7.43 (7.86 to 7.07) |
7.44 (7.77 to 7.93) |
7.45 | 7.26 | |
| μ | 1.21 (−0.11 to 2.55) |
7.62 (6.58 to 9.12) |
7.67 (6.93 to 8.42) |
7.33 | 7.34 | |
| 5’-MABN | ||||||
| κ | 0.95 (0.21 to 1.68) |
8.18 (9.81 to 7.53) |
8.09 (7.29 to 8.89) |
8.30 | 8.43 | |
| μ | 0.46 (−0.29 to 1.21) |
7.85 (6.58 to 9.12) |
8.09 (6.81 to 9.38) |
8.23 | 8.94 | |
Values expressed are mean ± 95% confidence interval of n=4 tissues, except where derived as single values.
For Schild plots the regression was linear and the slope was within 95% confidence interval for unity for all antagonists.
Gaddum–Schild model of orthosteric competitive antagonism was used to re-fit the data to a linear model constraining the slope to a value of exactly 1 and the pA2 determined.
Apparent pA2 estimates derived from Schild’s equation (pA2 = log (DR-1) - log [antagonist] and the lowest positive log (DR-1) value. were calculated from the lowest positive log (DR-1) value that corresponded to a significant rightward shift in the agonist pEC50 in the presence of the antagonist.