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Comparing sertindole to other new generation antipsychotics on preferential dopamine output in limbic versus striatal projection regions: Mechanism of action
Author(s) -
Hertel Peter
Publication year - 2006
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20322
Subject(s) - sertindole , aripiprazole , nucleus accumbens , quetiapine , antipsychotic , clozapine , pharmacology , ziprasidone , partial agonist , chemistry , dopamine receptor d2 , haloperidol , olanzapine , dopamine , agonist , neuroscience , medicine , psychology , schizophrenia (object oriented programming) , receptor , psychiatry
The effects of acute administration of sertindole on DA output were examined in the shell part of the nucleus accumbens (NACS) and the striatum (STR), areas which are associated with limbic functions and motor control, respectively, by using in vivo differential normal pulse voltammetry in rats. The effect of sertindole was compared to those obtained with the reference antipsychotic drugs clozapine and haloperidol, new generation antipsychotics represented by risperidone, olanzapine, ziprasidone, quetiapine, and aripiprazole, as well as, with those of preferential D 2/3 , D 4 , 5‐HT 1A , 5‐HT 2A , 5‐HT 2C , α 1 , and α 2 receptor ligands. In similarity with the new generation antipsychotics, sertindole preferentially increase DA output in the NACS as compared to the STR whereas the opposite was true for haloperidol. The regional specific effect of the partial D 2 receptor agonist aripiprazole was mainly driven by a decrease in striatal rather that by an increase in accumbal DA output. The selective 5‐HT 2A and D 4 receptor antagonists MDL100,151 and Lu 38‐012, respectively, both preferentially increased DA output in the NACS. Thus, the present results are in line with the hypothesis that 5‐HT 2A receptor antagonism is of importance for the observed limbic selectivity of new generation antipsychotics and, in turn, to their favorable clinical profile especially as regards extrapyramidal side effects (EPS) liability. For some compounds, blockade of D 4 receptors may also play a role in this regard. Synapse 60:543–552, 2006. © 2006 Wiley‐Liss, Inc.