TABLE 1

Binding affinities of N-methylscopolamine and novel selective agonists for M₁ mAChR mutants

The affinity constants pK_d (−log M) for [³H]NMS, NDMC, AC-42, and 77-LH-28-1 are tabulated. A cooperativity factor value α is specified where its inclusion significantly improved the global fit to an allosteric ternary complex model of ligand-[³H]NMS interaction (see Materials and Methods). Otherwise, the interactions seemed competitive. pK_d,NMS values were estimated using three different NMS concentrations, equivalent to 0.1, 2, and 10 times K_d are the means of five different experiments for each, and mutant ± S.E.M. pK_d values for the NSAs are the mean ± S.E.M. of measurements using three different [³H]NMS concentrations (0.1, 2, and 10 times K_d); slope factors of binding curves were close to 1.0.