Displacement of bound 14C-fluphenazine by biogenic amines and antipsychotic drugs in homogenates of brain tissue.

Abstract

CONSIDERABLE evidence suggests that antipsychotic drugs block dopamine receptors at postsynaptic sites in the central nervous system1,2. Receptor sites for neurotransmitter substances, such as acetylcholine3–5 and glycine6, have been studied by measurements of the direct binding of radiolabelled compounds that have high affinity for such sites and cause receptor blockade. In a similar study of biogenic amine receptor sites, I have measured the binding and displacement of the potent phenothiazine antipsychotic drug, fluphenazine, to preparations of brain tissue in vitro. I have found that fluphenazine binds to all regions of the rat brain, and that the potency of antipsychotic drugs in displacing fluphenazine correlates well with their clinical efficacy. Dopamine does displace fluphenazine from binding sites, but this is a nonspecific effect shared by other biogenic amines.