The authors investigated the effect of typical and atypical neuroleptics on dopamine transmission in the bed nucleus of stria terminalis (BNST) with concentric microdialysis probes in freely moving rats.Basal extracellular dopamine concentration in the BNST was not modified by the typical neuroleptics haloperidol and raclopride, whereas the atypical neuroleptics clozapine, risperidone, olanzapine, and BIMG 80 increased dopamine extracellular concentration with maximum increases observed 40 min after treatment.

01 Jul 1997·Journal of NeurochemistryQ2 · MEDICINE

BIMG 80, a Novel Potential Antipsychotic Drug: Evidence for Multireceptor Actions and Preferential Release of Dopamine in Prefrontal Cortex

Q2 · MEDICINE

Article

Author: Eugenia Monferini ; Monica Cerutti ; Marina Volonté ; Fabio Fodritto ; Franco Borsini

Abstract: In radioligand binding studies, BIMG 80, a new putative antipsychotic, displayed good affinity at certain serotonin (5‐HT1A, 5‐HT2A, 5‐HT6), dopamine (D1, D2L, D4), and noradrenergic (α1) receptors. The effect of acute subcutaneous BIMG 80, clozapine, haloperidol, risperidone, amperozide, olanzapine, and Seroquel was then investigated on dopamine release in medial prefrontal cortex, nucleus accumbens, and striatum in freely moving rats using the microdialysis technique. Four different neurochemical profiles resulted from the studies: (a) Systemic administration of BIMG 80, clozapine, and amperozide produced greater percent increases in dopamine efflux in medial prefrontal cortex than in the striatum or the nucleus accumbens. (b) Haloperidol induced a similar increase in dopamine concentrations in the striatum and nucleus accumbens with no effect in the medial prefrontal cortex. (c) Risperidone and olanzapine stimulated dopamine release to a similar extent in all brain regions investigated. (d) Seroquel failed to change significantly dopamine output both in the medial prefrontal cortex and in the striatum. Because an increase in dopamine release in the medial prefrontal cortex may be predictive of effectiveness in treating negative symptoms and in the striatum may be predictive of induction of extrapyramidal side effects, BIMG 80 appears to be a potential antipsychotic compound active on negative symptoms of schizophrenia with a low incidence of extrapyramidal side effects.

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Indication	Highest Phase	Country/Location	Organization	Date
Psychotic Disorders	Discovery	DE	Boehringer Ingelheim International GmbH	-

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