BIMG-80, A NOVEL POTENTIAL ANTIPSYCHOTIC DRUG - EVIDENCE FOR MULTIRECEPTOR ACTIONS AND PREFERENTIAL RELEASE OF DOPAMINE IN PREFRONTAL CORTEX

In radioligand binding studies, BIMG 80, a new putative antipsychotic, displayed good affinity at certain serotonin (5-HT1A, 5-HT2A, 5-HT6), dopamine (D-1, D-2L, D-4), and noradrenergic (alpha(1)) receptors. Th e effect of acute subcutaneous BIMG 80, clozapine, haloperidol, risper idone, amperozide, olanzapine, and Seroquel was then investigated on d opamine release in medial prefrontal cortex, nucleus accumbens, and st riatum in freely moving rats using the microdialysis technique. Four d ifferent neurochemical profiles resulted from the studies: (a) Systemi c administration of BIMG 80, clozapine, and amperozide produced greate r percent increases in dopamine efflux in medial prefrontal cortex tha n in the striatum or the nucleus accumbens, (b) Haloperidol induced a similar increase in dopamine concentrations in the striatum and nucleu s accumbens with no effect in the medial prefrontal cortex, (c) Risper idone and olanzapine stimulated dopamine release to a similar extent i n all brain regions investigated. (d) Seroquel failed to change signif icantly dopamine output both in the medial prefrontal cortex and in th e striatum, Because an increase in dopamine release in the medial pref rontal cortex may be predictive of effectiveness in treating negative symptoms and in the striatum may be predictive of induction of extrapy ramidal side effects, BIMG 80 appears to be a potential antipsychotic compound active on negative symptoms of schizophrenia with a low incid ence of extrapyramidal side effects.