Brain receptors for antipsychotic drugs and dopamine: direct binding assays.

In order to test the suggestion that antipsychotic drugs act by blocking dopamine receptors in the brain, the direct effects of such neuroleptic drugs were tested on the stereospecific binding of 3Hdopamine and of 3Hhaloperidol to rat brain striata and their subfractions. The stereospecific component of binding was defined as that amount of 3hdopamine or 3Hhaloperidol bound in the presence of (-)-butaclamol (an inactive drug) minus that bound in the presence of (+)-butaclamol (a potent neuroleptic drug); 100 nM butaclamol was used for the 3Hhaloperidol assay, while 1 muM butaclamol was used for the 3Hdopamine assay. Various antipsychotic drugs inhibited this stereospecific component in both the dopamine and haloperidol assays. These inhibitory potencies correlated with the clinical doses used for controlling schizophrenia.