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Titolo:
SIMULTANEOUS INCREASES OF EXTRACELLULAR MONOAMINES IN MICRODIALYSATESFROM HYPOTHALAMUS OF CONSCIOUS RATS BY DULOXETINE, A DUAL SEROTONIN AND NOREPINEPHRINE UPTAKE INHIBITOR
Autore:
ENGLEMAN EA; PERRY KW; MAYLE DA; WONG DT;
Indirizzi:
ELI LILLY & CO,LILLY CORP CTR,CENT NERVOUS SYST RES,LILLY RES LABS INDIANAPOLIS IN 46285
Titolo Testata:
Neuropsychopharmacology
fascicolo: 4, volume: 12, anno: 1995,
pagine: 287 - 295
SICI:
0893-133X(1995)12:4<287:SIOEMI>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; ENDOGENOUS NORADRENALINE RELEASE; EPILEPSY-PRONE RATS; 5-HYDROXYINDOLEACETIC ACID; TRANSCORTICAL DIALYSIS; BIOCHEMICAL PROFILE; INVIVO DIALYSIS; FRONTAL-CORTEX; BRAIN; 5-HYDROXYTRYPTAMINE;
Keywords:
MICRODIALYSIS; HYPOTHALAMUS; RATS; MONOAMINES; UPTAKE INHIBITORS; HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Physical, Chemical & Earth Sciences
Physical, Chemical & Earth Sciences
Physical, Chemical & Earth Sciences
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
34
Recensione:
Indirizzi per estratti:
Citazione:
E.A. Engleman et al., "SIMULTANEOUS INCREASES OF EXTRACELLULAR MONOAMINES IN MICRODIALYSATESFROM HYPOTHALAMUS OF CONSCIOUS RATS BY DULOXETINE, A DUAL SEROTONIN AND NOREPINEPHRINE UPTAKE INHIBITOR", Neuropsychopharmacology, 12(4), 1995, pp. 287-295

Abstract

Duloxetine (LY248686, thyl-3-(1-napthalenyloxy)-2-thiophene-propanamine) is a potent dual inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) uptake in hypothalamus and cerebral cortex of rat brain (Wong et al. 1993; Fuller et al. 1994). Consistent with the dual mechanisms of inhibiting 5-HT and NE uptake, duloxetine at 15 mg/kg IP produced large increases in extracellular levels of 5-HT (250%) and NE (1,100%) 30 minutes after systemic administration. Levels of 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), metabolites of NE and 5-HT, respectively, were reduced, whereas those of dopamine (DA) and ifs metabolite 3, 4-dihydroxyphenylacetic acid(DOPAC) were not significantly altered. Duloxetine at 7 mg/kg produced less pronounced increases while no consistent effectswere observed at 4 mg/kg. In this dose range, duloxetine inhibited 5-HT uptake in platelets ex vivo without inhibiting striatal dopamine (DA) uptake. In the present study we also found that the primary amine (a racemate) of duloxetine is about one-fourth as active as duloxetine to inhibit 5-HT and NE uptake. The potential primary amine metabolite of duloxetine might contribute, in part, to the inhibition of 5-HT andNE uptake in vivo. Thus the ability to produce robust increases of extracellular 5-HT and NE levels suggests that duloxetine may potentially be a highly effective antidepressant agent.

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Documento generato il 23/09/20 alle ore 14:34:16