Parameters characterizing the allosteric interactions of the test ligands and [3H]NMS at the M2 receptor
The ratios of affinities (pEC50,diss - pKA) were calculated from affinity for the [3H]NMS-occupied receptor (pEC50,diss) and free receptor (pKA) and compared with the negative log cooperativity factor (pα) as determined in the kinetic allosteric ternary complex model.
| pEC50,diss | pKA | pEC50,diss - pKA | pα | α | |
|---|---|---|---|---|---|
| THRX-160209 | 6.5 | 10.2 | −3.7 | −3.4 | 2547 |
| W84 | 7.2 | 8.0 | −0.8 | −0.8 | 6.9 |
| Gallamine | 6.2 | 8.2 | −2.0 | −1.7 | 45 |
pEC50diss, negative log value of the concentration reducing [3H]NMS dissociation by 50% determined using excess ligand dissociation assays; pKA, negative log value of the equilibrium dissociation constant for test compounds binding to unoccupied receptors determined from nonequilibrium radioligand binding assays; pα, negative log value of the cooperativity factor (α) determined from nonequilibrium radioligand binding assays.