Document Detail


Mechanisms of action of current and potential pharmacotherapies of obsessive-compulsive disorder.
MedLine Citation:
PMID:  16427729     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A significant body of evidence documented that the orbitofrontal cortex (OFC) and the head of caudate nucleus are involved in the mediation of obsessive-compulsive disorder (OCD) symptoms. Potent serotonin (5-HT) reuptake inhibitors (SRIs) are the only antidepressant agents thus far shown to be effective in the treatment of OCD. The present review summarizes information on 5-HT release and the adaptive changes in pre- and postsynaptic 5-HT receptors sensitivity induced by SRI treatment in rat and guinea pig structures involved in OCD. It emphasizes that the time course for the occurrence of increased 5-HT release and terminal 5-HT1D desensitization is congruent with the delayed therapeutic response to SRI in OCD. In addition, a greater dose of SRI inducing a greater degree of reuptake inhibition may play an essential role in this phenomenon. This is consistent with the common clinical observation that high doses of SRIs are sometimes necessary to obtain an anti-OCD effect, and with the results of some fixed-dose double blind trials showing a dose-dependent therapeutic effect of SRIs. It is hypothesized that enhanced 5-HT release in the OFC is mediated by the activation of normosensitive postsynaptic 5-HT2-like receptors and underlies the therapeutic action of SRI in OCD. This is supported by the beneficial effect of some hallucinogens with 5-HT2 agonistic properties in obtaining a more rapid therapeutic response. Finally, based on this knowledge, new strategies aimed at producing more rapid, effective and safe anti-OCD drugs, such as a selective action on terminal 5-HT1D receptors, on 5-HT2 receptors as well as on the glutamate system, are discussed.
Authors:
Mostafa El Mansari; Pierre Blier
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Publication Detail:
Type:  Journal Article; Review     Date:  2006-01-20
Journal Detail:
Title:  Progress in neuro-psychopharmacology & biological psychiatry     Volume:  30     ISSN:  0278-5846     ISO Abbreviation:  Prog. Neuropsychopharmacol. Biol. Psychiatry     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-04-21     Completed Date:  2006-07-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8211617     Medline TA:  Prog Neuropsychopharmacol Biol Psychiatry     Country:  England    
Other Details:
Languages:  eng     Pagination:  362-73     Citation Subset:  IM    
Affiliation:
University of Ottawa Institute of Mental Health Research, Lady Grey Building, 1145 Carling Avenue, Ottawa, ON, Canada K1Z 7K4.
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MeSH Terms
Descriptor/Qualifier:
Frontal Lobe / drug effects*,  pathology,  physiopathology
Humans
Models, Neurological
Neurons / drug effects,  physiology
Obsessive-Compulsive Disorder / drug therapy*,  metabolism,  pathology
Serotonin / metabolism
Serotonin Uptake Inhibitors / pharmacology*,  therapeutic use
Synapses / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Serotonin Uptake Inhibitors; 50-67-9/Serotonin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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