Neuropharmacological effects of low and high doses of repeated oral dexfenfluramine in rats: a comparison with fluoxetine.
Pharmacol Biochem Behav
; 57(4): 851-6, 1997 Aug.
Article
em En
| MEDLINE
| ID: mdl-9259015
The neuropharmacological effects of repeated oral doses of dexfenfluramine (DF; 1.25-10 mg/kg, twice daily for 21 days) were examined in rats and related to the drug brain levels. Results were compared with fluoxetine (FL) given at similar doses relative to its anorectic ED50. Both drugs dose-dependently slowed body weight gain and reduced brain serotonin (5-HT). However, at 1.25 mg/kg DF caused only a slight and transient decrease in cortical 5-HT. Comparable doses of FL (6.25-12.5 mg/kg) lowered 5-HT more than DF, besides slightly reducing striatal dopamine. At higher doses DF markedly reduced 5-HT in all regions, and to a lesser extent noradrenaline in hippocampus. There was a negative relationship between 5-HT and log total active drug levels and the indole was approximately halved at drug levels about 50 times lower with DF than FL. However, the ratio between drug levels causing marked 5-HT reductions and those considered anorectic was similar for DF and FL because brain levels at the anorectic ED50 were higher with FL than DF. Long-lasting reductions of 5-HT were also observed but recovery was only consistently slow beginning from 5 mg/ kg DF. Comparable doses of FL could not be used because its general toxicity leads to the death of rats after only 2-4 multiples of its anorectic ED50.
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Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Depressores do Apetite
/
Fluoxetina
/
Inibidores Seletivos de Recaptação de Serotonina
/
Fenfluramina
Limite:
Animals
Idioma:
En
Revista:
Pharmacol Biochem Behav
Ano de publicação:
1997
Tipo de documento:
Article