Document Detail


Serotonin releasing agents. Neurochemical, therapeutic and adverse effects.
MedLine Citation:
PMID:  11888573     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This review summarizes the neurochemical, therapeutic and adverse effects of serotonin (5-HT) releasing agents. The 5-HT releaser (plus minus)-fenfluramine is composed of two stereoisomers, (+)-fenfluramine and (minus sign)-fenfluramine, which are N-de-ethylated to yield the metabolites, (+)-norfenfluramine and (minus sign)-norfenfluramine. Fenfluramines and norfenfluramines are 5-HT transporter substrates and potent 5-HT releasers. Other 5-HT releasing agents include m-chlorophenylpiperazine (mCPP), a major metabolite of the antidepressant drug trazodone. Findings from in vitro and in vivo studies support the hypothesis that fenfluramines and mCPP release neuronal 5-HT via a non-exocytotic carrier-mediated exchange mechanism involving 5-HT transporters. (+)-Norfenfluramine is a potent 5-HT(2B) and 5-HT(2C) receptor agonist. The former activity may increase the risk of developing valvular heart disease (VHD), whereas the latter activity is implicated in the anorectic effect of systemic fenfluramine. Anorectic agents that increase the risk of developing primary pulmonary hypertension (PPH) share the common property of being 5-HT transporter substrates. However, these drugs vary considerably in their propensity to increase the risk of PPH. In this regard, neither trazodone nor mCPP is associated with PPH. Similarly, although some 5-HT substrates can deplete brain 5-HT (fenfluramine), others do not (mCPP). In addition to the established indication of obesity, 5-HT releasers may be helpful in treating psychiatric problems such as drug and alcohol dependence, depression and premenstrual syndrome. Viewed collectively, it seems possible to develop new medications that selectively release 5-HT without the adverse effects of PPH, VHD or neurotoxicity. Such agents may have utility in treating a variety of psychiatric disorders.
Authors:
Richard B Rothman; Michael H Baumann
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Pharmacology, biochemistry, and behavior     Volume:  71     ISSN:  0091-3057     ISO Abbreviation:  Pharmacol. Biochem. Behav.     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-03-12     Completed Date:  2002-09-11     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0367050     Medline TA:  Pharmacol Biochem Behav     Country:  United States    
Other Details:
Languages:  eng     Pagination:  825-36     Citation Subset:  IM    
Affiliation:
Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, P.O. Box 5180, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. rrothman@intra.nida.nih.gov
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MeSH Terms
Descriptor/Qualifier:
Animals
Appetite Depressants / adverse effects,  pharmacology,  therapeutic use
Brain Chemistry / drug effects*
Fenfluramine / adverse effects,  pharmacology,  therapeutic use
Humans
Serotonin / metabolism*
Serotonin Agents / adverse effects,  pharmacology*,  therapeutic use
Chemical
Reg. No./Substance:
0/Appetite Depressants; 0/Serotonin Agents; 458-24-2/Fenfluramine; 50-67-9/Serotonin

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


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