Regional selectivity of neuroleptic drugs: an argument for site specificity.

Differences among neuroleptic drugs in their abilities to produce extrapyramidal side-effects have alternatively been ascribed to their inherent anticholinergic effect or their preferential action with particular brain areas. Animal behavioral studies in rats, with the intralimbic or intrastriatal injection of dopamine demonstrate that atypical neuroleptics, i.e., clozapine, thioridazine, show a greater relative preference for blocking dopamine's limbic actions. Studies using the rat model of tardive dyskinesia (neuroleptic-induced behavioral hypersensitivity), suggest that the atypical neuroleptics are again unique. Receptor ligand studies in rat brain and human brain, using 3H-spiroperidol, show that haloperidol produces a preferential blockade of striatal receptor sites, whereas clozapine and thioridazine are most active at limbic sites. Biochemical data in animals and clinical data in man are reviewed to further support the concept of site specificity.