Linked Life Data

1738103

Source:http://linkedlifedata.com/resource/pubmed/id/1738103

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1992-3-17
pubmed:abstractText
Fluoxetine, an antidepressant and inhibitor of serotonin reuptake, was evaluated as an anticonvulsant in genetically epilepsy-prone rats (GEPRs) because seizure predisposition in GEPRs is partially dependent on deficits in brain serotonin. Fluoxetine produced dose-dependent reductions in sound-induced convulsion intensity in both moderate seizure GEPRs and severe seizure GEPRs with the peak anticonvulsant effect occurring 4 hr after i.p. administration. A subchronic study in severe seizure GEPRs demonstrated that the ED50 after 28 days of dosing (8.2 mg/kg) was lower than the acute ED50 (15.9 mg/kg) so that there was no apparent development of tolerance. The lower ED50 after subchronic administration apparently resulted from accumulation of fluoxetine and its metabolite norfluoxetine in brain. Brain microdialysis studies showed that acute fluoxetine administration resulted in a significant increase in extracellular serotonin concentration in the thalamus. The increase in serotonin concentration in the dialysate corresponded temporally with the anticonvulsant effect produced by fluoxetine. Intrathalamic administration of fluoxetine via the dialysis probe caused an increase in serotonin concentration in the dialysate, suggesting that the effect of fluoxetine was on nerve terminals. Fluoxetine could be dialyzed from thalamus after its i.p. administration. Fluoxetine concentration in the thalamic dialysate was similar to the concentration found in plasma. We conclude that fluoxetine is an effective anticonvulsant in GEPRs and that the microdialysis results strongly suggest a relationship between the effects of fluoxetine on serotonergic neurons and the anticonvulsant effect produced by this drug.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
260
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
533-40
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Effects of fluoxetine on convulsions and on brain serotonin as detected by microdialysis in genetically epilepsy-prone rats.
pubmed:affiliation
Department of Basic Sciences, University of Illinois College of Medicine, Peoria.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't