Document Detail

A perspective on the new mechanism of antidepressants: neuritogenesis through sigma-1 receptors.
MedLine Citation:
PMID:  15547787     Owner:  NLM     Status:  MEDLINE    
Sigma receptors were first described as one of the opiate receptor subtypes. Now it is well established that sigma receptors, existing as subtypes sigma-1 and sigma-2, are unique non-opioid receptors which are implicated in higher-ordered brain functions. Sigma-1 receptors have high to moderate affinities for (+)benzomorphans and also many psychotrophic drugs and neurosteroids. Sigma-1 receptor agonists and certain neurosteroids such as dehydroepiandrosterone sulfate (DHEA-S) have antidepressant-like effects in animal behavioral models of depression. The antidepressant-like effect induced by sigma-1 receptor agonists may involve intracellular Ca (2+) mobilization such that sigma-1 receptor agonists modulate Ca (2+) release from endoplasmic reticulum (ER) in a cytoskeletal protein-dependent manner. In addition, growth factor-induced neurite outgrowth is mediated through sigma-1 receptors, suggesting a role of antidepressants in neuroplasticity. Igmesine (JO1783), OPC-14 523 and SA4503, have recently been developed as sigma-1 agonists and are found to have antidepressant-like activity perhaps with fewer side effects. This article reviews the new potential use of sigma-1 receptor ligands in the treatment of mood disorder.
M Takebayashi; T Hayashi; T-P Su
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Pharmacopsychiatry     Volume:  37 Suppl 3     ISSN:  0176-3679     ISO Abbreviation:  Pharmacopsychiatry     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-11-19     Completed Date:  2005-02-04     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  8402938     Medline TA:  Pharmacopsychiatry     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  S208-13     Citation Subset:  IM    
Cellular Pathobiology Unit, Cellular Neurobiology Research Branch, National Institute on Drug Abuse, NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
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MeSH Terms
Antidepressive Agents / pharmacology,  therapeutic use*
Binding Sites / drug effects
Calcium / metabolism
Depression / drug therapy*
Disease Models, Animal
Drug Interactions
Endoplasmic Reticulum / drug effects,  metabolism
Mental Disorders / drug therapy
Receptors, sigma / agonists,  physiology*
Steroids / pharmacokinetics
Reg. No./Substance:
0/Antidepressive Agents; 0/Receptors, sigma; 0/Steroids; 0/sigma-1 receptor; 7440-70-2/Calcium

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

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