Linked Life Data

2463643

Source:http://linkedlifedata.com/resource/pubmed/id/2463643

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1989-2-23
pubmed:abstractText
d-Fenfluramine is an anorectic drug believed to act by enhancement on serotonergic function in the brain. d-Fenfluramine (or the racemate) releases serotonin through a carrier-dependent mechanism, and serotonin release is the mechanism usually thought to produce its serotonergic effects. However, d-fenfluramine also inhibits serotonin uptake in vitro, and serotonin uptake inhibition is sometimes suggested to contribute to its mechanism of anorectic activity. Neurochemical experiments were done to examine serotonin release and serotonin uptake inhibition as mechanisms of action of d-fenfluramine in rats and to compare d-fenfluramine to fluoxetine, a serotonin uptake inhibitor. d-Fenfluramine decreased serotonin concentration in rat brain as early as 1 hr; at 1 hr 5-hydroxyindoleacetic acid (5HIAA) concentration was slightly increased, but at later times 5HIAA was also decreased. Fluoxetine, in contrast, did not change serotonin concentration in whole brain but decreased 5HIAA concentration at all time points. At all time intervals studied, the 5HIAA/serotonin ratio was increased by d-fenfluramine (and by Ro 4-1284, a nonspecific serotonin releaser) but was decreased by fluoxetine, a serotonin uptake inhibitor. No decrease in 5HIAA concentration or in the 5HIAA/serotonin ratio was apparent at any time or after any dose of d-fenfluramine studied. The possibility that doses of d-fenfluramine below those needed for serotonin release might inhibit serotonin uptake was tested by determining whether d-fenfluramine could block the acute depletion of brain serotonin by p-chloroamphetamine, or the long-term neurotoxic effect of p-chloroamphetamine on brain serotonin neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0091-3057
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
715-21
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Mechanisms of effects of d-fenfluramine on brain serotonin metabolism in rats: uptake inhibition versus release.
pubmed:affiliation
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
pubmed:publicationType
Journal Article