An in vivo study of the binding of the neuroleptic drugs spiroperidol and bromospiroperidol has indicated a large amount of specific binding to the dopamine‐rich caudate nuclei of the murine brain. We have tested the applicability of the simple thermodynamic equilibrium equation to describe this binding and find that it seems to be a reasonable description of the process. It appears that a period of several hours is needed for reaching equilibrium, but after that time the behavior appears slowly to follow the equilibrium isotherm. One consequence of this model is the apparent competition of endogenous dopamine for the binding sites in vivo. The data can only be fitted by the calculations when the endogenous dopamine is included as a competitive ligand. This competition presents the interesting possibility of measuring the synaptic dopamine concentration by its effect on the binding of neuroleptic drugs. A second observation in these studies was the increase of nonspecific binding of bromospiroperidol at very low drug loadings. This increase is attributed to the presence of binding sites that are ubiquitously dispersed and very dilute but of high affinity.
Annals of Neurology – Wiley
Published: Jan 1, 1984
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