TABLE 1

Binding parameters for test compounds at EGFP(Δ17)hM1 receptors determined from FRET studies using Bodipy-pirenzepine tracers

Drug affinity constants (−log M; mean ± S.E. values for 3–4 separate determinations) are from analyses of saturation (Kd, eq. 1), displacement (competitive model: Ki, eq. 4; allosteric model: Kx, cooperativity factor α, eq. 5), and off-rate (EC50,diss, Emax,diss given in parentheses, eq. 8) experiments (Materials and Methods; Data Analyses).

Bo(10)PzBo(12)PzBo(15)PzBo(22)Pz
pKd,i,x, pαpEC50,diss (Emax,diss, %)pKd,i,x, pαpEC50,diss (Emax,diss, %)pKd,ipKd,i
Tracer7.91 ± 0.047.67 ± 0.017.97 ± 0.017.92 ± 0.09
Atropine8.89 ± 0.06a9.02 ± 0.049.10 ± 0.038.92 ± 0.06
Pirenzepine7.70 ± 0.06a7.96 ± 0.068.25 ± 0.047.96 ± 0.08
Gallamine4.79 ± 0.033.44 ± 0.054.82 ± 0.053.47 ± 0.044.68 ± 0.074.68 ± 0.06
−1.04 ± 0.06b(80 ± 4)−1.09 ± 0.07b(92 ± 5)
Brucine4.25 ± 0.05c4.45 ± 0.044.32 ± 0.085.04 ± 0.044.27 ± 0.074.21 ± 0.04
0.20 ± 0.05b,c(93 ± 3)0.68 ± 0.05b(94 ± 2)

  • ↵a Values are from Ilien et al., 2003.

  • ↵b Cooperativity factor α (negative logarithm).

  • ↵c Because of nearly neutral cooperativity, EC50,diss was used for curve fitting according to eq. 5 as described in Data Analyses.