SIMUL: an accurate method for the determination of receptor subtype proportions using a personal computer

Many tissues possess two classes of binding sites for a drug. To estimate the proportions of each it is necessary either to use selective ligands or to perform competition experiments in which the binding of a radioligand is inhibited by a selective unlabeled ligand. However, this method will only be accurate provided the radioligand is non-selective. A selectivity of 2- to 3-fold for one receptor may produce errors of 50% or more in the estimates, depending on the concentration of radioligand chosen. Since most ligands are selective to some extent simple estimates will often provide inaccurate information. The computer program described here (SIMUL) determines the proportions of receptor subtypes by considering the relative affinities of the competing agent for the receptor subtypes, the selectivity of the radioligand and their associated concentrations.