期刊
EUROPEAN PSYCHIATRY
卷 20, 期 1, 页码 15-27出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.eurpsy.2004.11.003
关键词
antipsychotic drugs; dopamine; glutamate; schizophrenia; PET; SPECT
类别
资金
- NIMH NIH HHS [K02MH01603-01, K08 MH01594-01, K02 MH064178-01A2] Funding Source: Medline
- NATIONAL INSTITUTE OF MENTAL HEALTH [K02MH001603, K08MH001594, K02MH064178] Funding Source: NIH RePORTER
Multiple lines of evidence including recent imaging studies suggest that schizophrenia is associated with an imbalance of the dopaminergic system, entailing hyperstimulation of striatal dopamine (DA) D-2 receptors and understimulation of cortical DA D, receptors. This DA endophenotype presumably emerges from the background of a more general synaptic dysconnectivity involving alterations in N-methyl-D-aspartate (NMDA) and glutamatergic (GLU) functions. Equally important is the fact that this DA dysregulation might further impair NMDA transmission. The first generation antipsychotic (FGA) drugs are characterized by high affinity to and generally high occupancy of D-2 receptors. The efficacy of FGAs is limited by a high incidence of extrapyramidal side-effects (EPS). Second generation antipsychotic (SGA) drugs display reduced EPS liability and modest but clinically significant enhanced therapeutic efficacy Compared to FGAs. the improved therapeutic action of SGAs probably derives from a more moderate D-2 receptor blockade. We will review the effects of SGAs on other neurotransmitter systems and conclude by highlighting the importance of therapeutic strategies aimed at directly increasing prefrontal DA, D-1 receptor transmission or NMDA transmission to enhance the therapeutic effect of moderate D-2 receptor antagonism. (C) 2004 Elsevier SAS. All rights reserved.
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