Pharmacodynamics
Single Ligand Receptor Binding



The form of the typical ligand-binding and dose-response curves follows from the law of mass action and can be mathematically derived. Briefly, the formation of ligand-receptor complexes (Xe) is a function of the amount of ligand (A), the number of receptors (rt), and the association (k1) and dissociation (k2) rate constants. The equation is simplified by calculating the dissociation constant (K = k2/k1) which describes the tendency for the ligand to become dissociated from the receptor. This is numerically related to affinity (1/K) which is the more commonly reported variable in psychopharmacological applications.

This function is applicable for a wide variety of ligand-receptor interactions and provides the theoretical basis for standard dose-response analysis. Ligand doses are usually expressed as log(dose) and receptor binding or biological effect is normally plotted on a linear scale. Empirical data conforming to this theoretically derived function have particularly strong intrinsic validity. Notable exceptions to this model include allosteric receptor binding and certain pharmacodynamic drug interactions.

The following simulation assumes a simple bimolecular model. In cases where efficacy = 1, the biological response should directly follow the binding function. Compare the figure generated by this function with the shape of a typical dose-response curve.
 
Simulation Parameters
K = 0.003  Concentration (A) =
0.3 log unit increments
A * rt
Xe = -------
A + K
Receptors (rt) = 100
Ligand
Concentration
% Maximum
Binding
0.0001 3.2
0.0002 6.3
0.0004 11.8
0.0008 21.1
0.0016 34.8
0.0032 51.6
0.0064 68.1
0.0128 81.0
0.0256 89.5
0.0512 94.5
0.1024 97.2
0.2048 98.6
0.4096 99.3
0.8192 99.6

The data are plotted in the following graph. 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 portion of the curve between 20% (A20) and 80% (A80) of the maximum binding is linear.
ChartObject Chart 1
 


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