Pharmacodynamics
Ligands with Different Affinities


The following simulations compare three ligands with three different dissociation constants (i.e., affinities). Note that the functions are all parallel with potency ratios equal to KB/KA and KC/KB (i.e., 10) and to KC/KA (i.e., 100). Compare these values with the A50 for each ligand extrapolated from the table. The actual A50s would be calculated by performing linear regression on the data from A20 to A80.
 
Simulation Parameters
Ligand
K
1/K
Drug-A 0.003 333.33
[An] = log[An-1] + 0.3 Drug-B 0.030 33.33
rt = 100 Drug-C 0.300 3.33
% Maximum Binding
Ligand
Concentration		 Drug-A Drug-B Drug-C
0.0001 3.2 0.3 0.0
0.0002 6.3 0.7 0.1
0.0004 11.8 1.3 0.1
0.0008 21.1 2.6 0.3
0.0016 34.8 5.1 0.5
0.0032 51.6 9.6 1.1
0.0064 68.1 17.6 2.1
0.0128 81.0 29.9 4.1
0.0256 89.5 46.0 7.9
0.0512 94.5 63.1 14.6
0.1024 97.2 77.3 25.4
0.2048 98.6 87.2 40.6
0.4096 99.3 93.2 57.7
0.8192 99.6 96.5 73.2
1.6384 99.8 98.2 84.5
3.2768 99.9 99.1 91.6
6.5536 100.0 99.5 95.6
13.1072 100.0 99.8 97.8
26.2144 100.0 99.9 98.9

The data are plotted in the following graph, beginning with Drug-A on the far left, Drug-B in the middle, and Drug-C on the far right. The ligand concentration is expressed on a log scale, but the listed values are misleading (i.e., they represent successive log[dose]-increments not actual log[dose]). Note that the same effect can be produced by each ligand, but that the amount of ligand necessary to obtain any given level of effect is dependent on its dissociation constant. The ligand concentration producing 50% of the maximum binding or effect (A50) is frequently used as an indication of ligand potency, and potency comparisons across ligands usually use this reference point.
ChartObject Chart 2
 


Copyright 1999 Michael A. Bozarth
This page was last updated 28 October 1999 14:12 EDT
Report technical problems to: bozarth@buffalo.edu