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.