The possible role of dopamine autoreceptors in neuroleptic atypicality

Different brain pathways have been shown to subserve the therapeutic effects of neuroleptics and their extrapyramidal side effects. Agents which can discriminate between these pathways, therefore, might be able to produce 'atypical' clinical effects. Molindone, a novel neuroleptic of the indoleamine class, has been shown in basic paradigms to discriminate between brain dopaminergic systems by virtue of its ability to preferentially inhibit dopamine autoreceptors (DARs). Clinical studies suggest that molindone may be less likely than traditional neuroleptics to induce tardive dyskinesia and that molindone may preferentially ameliorate some negative schizophrenic symptoms. We suggest that the distinct clinical effects of molindone result from its ability to block DARs.