Low dose raclopride spares the extrapyramidal system in rat brain from metabolic effects

Frank I. Tarazi, Osamu Shirakawa, Carol A. Tamminga

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


The effect of a highly selective dopamine D2 receptor antagonist, raclopride ((-)-(S)-3,5-dichloro-N-(1-ethyl-2-pyrrolidinyl) methyl-6-methoxysalicylamide tartrate), on regional cerebral glucose metabolism in rat brain was determined using [14C]2-deoxyglucose autoradiography, and compared to a typical neuroleptic, haloperidol. Based on preclinical biochemistry and early clinical trial reports, it was hypothesized that raclopride would fail to functionally affect brain regions putatively involved with motor function, while altering psychosis-related regions. Raclopride at a low dose (1.5 mg/kg) significantly reduced regional cerebral glucose metabolism in neocortical areas. It showed a trend toward a similar reduction in limbic structures. But the drug did not have an effect in the extrapyramidal system at this dose. While, at a higher dose, raclopride (10.0 mg/kg), significantly reduced regional glucose metabolism throughout the susceptible grey matter areas of the brain including extrapyramidal regions, an effect similar to haloperidol. Based on approximate antipsychotic dose equivalence between haloperidol and raclopride, the clinically relevant low dose used in this study, failed to functionally alter metabolism in motor regions of brain while exerting a haloperidol-like effect in other areas traditionally linked to cognitive and affective behaviors. This suggests that a low dose of raclopride can exert regionally selective actions. The high dose of raclopride is metabolically active in all brain areas, and, therefore, in clinical application might produce involuntary motor syndromes, like parkinsonism and late onset dyskinesias, along with its antipsychotic effects.

Original languageEnglish (US)
Pages (from-to)71-77
Number of pages7
JournalEuropean Journal of Pharmacology
Issue number1
StatePublished - Feb 23 1993


  • Benzamides
  • Cerebral glucose metabolism (regional)
  • Neuroleptics
  • Raclopride

ASJC Scopus subject areas

  • Pharmacology


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