title: Functional effects of antipsychotic drugs: comparing clozapine with haloperidol.
abstract: BACKGROUND
  Using positron emission tomography (PET) with (15)O water, we compared regional cerebral blood flow (rCBF) patterns induced by clozapine or haloperidol in individuals with schizophrenia. Based on the known clinical characteristics of each drug, we hypothesized that brain regions where the drugs show similar rCBF patterns are among those mediating their antipsychotic actions; whereas, regions where the drugs produce different rCBF patterns are among those mediating their different drug actions, namely, haloperidol's motor side effects or clozapine's unique therapeutic action.
  
  
  METHODS
  Persons with schizophrenia were scanned using PET with (15)O water, first after withdrawal of all psychotropic medication (n = 6), then again after treatment with therapeutic doses of haloperidol (n = 5) or clozapine (n = 5).
  
  
  RESULTS
  Both drugs increased rCBF in the ventral striatum and decreased rCBF in hippocampus and ventrolateral frontal cortex. The rCBF increase associated with haloperidol was greater than that with clozapine in the dorsal and ventral striatum; the rCBF increase with clozapine was greater than that with haloperidol in cortical regions, including anterior cingulate and dorsolateral frontal cortex.
  
  
  CONCLUSIONS
  These data suggest that the rCBF increase in ventral striatum and/or the decrease in hippocampus and/or ventrolateral frontal cortex mediate a common component of antipsychotic action of these drugs. The increased rCBF in dorsal striatum by haloperidol could well be associated with its prominent motor side effects, whereas the increased rCBF in the anterior cingulate or dorsolateral frontal cortex may mediate the superior antipsychotic action of clozapine. The proposals based on these preliminary observations require further study.
authors.affiliation: Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA.
authors.forename: Adrienne C
authors.initials: AC
authors.lastname: Lahti
authors.forename: Henry H
authors.initials: HH
authors.lastname: Holcomb
authors.forename: Martin A
authors.initials: MA
authors.lastname: Weiler
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Medoff
authors.forename: Carol A
authors.initials: CA
authors.lastname: Tamminga
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010104:Oxygen Radioisotopes; D014055:Tomography, Emission-Computed
chemical_list: D014150:Antipsychotic Agents; D010104:Oxygen Radioisotopes; D003024:Clozapine; D006220:Haloperidol