| Assessment of 5-hydroxytryptamine efflux in rat brain during a mild, moderate and severe serotonin-toxicity syndrome. | |
| | |
MedLine Citation:
|
PMID: 19464285 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Serotonin (5-hydroxytryptamine; 5-HT)-toxicity syndrome, an iatrogenic brain disorder induced by excessive efflux of 5-HT, has received much attention because of increasing incidents of serotonergic antidepressants. However, the neural mechanism by which extracellular 5-HT is elevated to a toxic level for the syndrome remains to be determined. The goal of the present study was to test the hypothesis that extracellular 5-HT is composed of two component effluxes responsible for distinct aspects of the syndrome. The first set of experiments was to characterize the syndrome by measuring changes in neuromuscular signs, body-core temperature and mortality rate. Our results indicate that the syndrome severity can be categorized into mild, moderate and severe levels. The second set of experiments was to determine a threshold of extracellular 5-HT for induction of each level of the syndrome. Our results demonstrate that there were an 11-fold increase in the mild syndrome and an over 55-fold increase in the severe syndrome. In the last series of experiments, the excessive increases in 5-HT were pharmacologically separated into primary and secondary component effluxes with the 5-HT2A receptor antagonists cyproheptadine and ketanserin and NMDA receptor antagonist (+)-MK-801. Our results suggest that the primary component efflux was caused by direct drug effects on 5-HT biosynthetic and metabolic pathways and secondary efflux ascribed to indirect drug effect on a positive-feedback circuit involving 5-HT2A and NMDA receptors. In summary, the primary efflux could be an initial cause for the induction of the syndrome while the secondary efflux might involve deterioration of the syndrome. |
| | |
Authors:
|
Gongliang Zhang; Swapna Krishnamoorthy; Zhiyuan Ma; Nick P Vukovich; Xupei Huang; Rui Tao |
Related Documents
:
|
557755 - Elevated manganese levels associated with dementia and extrapyramidal signs. 8335455 - Constrictive pericarditis simulating intestinal lymphangiectasia in a patient with the ... 1603915 - Spanish toxic oil syndrome: ten years after the disaster. 17363955 - Soluble fas ligand: is it a critical mediator of toxic epidermal necrolysis and stevens... 22503355 - Prevalence of metabolic syndrome in patients with schizophrenia in india. 16909395 - Peters plus syndrome is caused by mutations in b3galtl, a putative glycosyltransferase. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-05-20 |
Journal Detail:
|
Title: European journal of pharmacology Volume: 615 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2009 Aug |
Date Detail:
|
Created Date: 2009-06-26 Completed Date: 2009-11-10 Revised Date: 2010-09-27 |
Medline Journal Info:
|
Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 66-75 Citation Subset: IM |
Affiliation:
|
Charles E. Schmidt College of Biomedical Science, Florida Atlantic University, 777 Glades Road, Boca Raton, Florida 33431, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
5-Hydroxytryptophan
/
metabolism* Animals Antidepressive Agents / toxicity Body Temperature / drug effects Clorgyline / toxicity Cyproheptadine / pharmacology Disease Models, Animal Dizocilpine Maleate / pharmacology Dose-Response Relationship, Drug Ketanserin / pharmacology Male Microdialysis Prefrontal Cortex / drug effects*, metabolism Rats Rats, Sprague-Dawley Receptor, Serotonin, 5-HT2A / antagonists & inhibitors Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors Serotonin / metabolism* Serotonin Syndrome / chemically induced, metabolism*, physiopathology |
| Grant Support | |
ID/Acronym/Agency:
|
DA14541/DA/NIDA NIH HHS; R01 DA014541-06/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antidepressive Agents; 0/Receptor, Serotonin, 5-HT2A; 0/Receptors, N-Methyl-D-Aspartate; 129-03-3/Cyproheptadine; 17780-72-2/Clorgyline; 50-67-9/Serotonin; 56-69-9/5-Hydroxytryptophan; 74050-98-9/Ketanserin; 77086-22-7/Dizocilpine Maleate |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Isoflurane induces a postconditioning effect on bovine pulmonary arterial endothelial cells exposed ...
Next Document: Adenosine: an endogenous modulator of innate immune system with therapeutic potential.