Simultaneous Increases of Extracellular Monoamines in Microdialysates from Hypothalamus of Conscious Rats by Duloxetine, a Dual Serotonin and Norepinephrine Uptake Inhibitor

Abstract

Duloxetine (LY248686, [ + J-N-methyl-3-(1-napthalenyloxy)-2-thiophene-propanamine) is a potent dual inhibitor of serotonin 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 duloxetine Guan and McBride 1988;Marsden et al. 1979). Applications of in vivo techniques (including rnicrodialysis) have demonstrated that extracellular serotonin in most rat brain areas increases several fold over basal levels upon systemic administration of serotonin uptake inhibitors, including fluoxetine (Auerbach et al.

Intranasal administration of nanostructured lipid carriers containing CNS acting drug: Pharmacodynamic studies and estimation in blood and brain

“…The administration of DLX increases the extracellular level of serotonin and NE (norepinephrine) in the rat frontal cortex and hypothalamus (Engleman et al, 1995). It blocks the reuptake of neurotransmitter molecules (serotonin and NE) back into the presynaptic neuron, leaving the molecules in the synaptic gap for longer period of time.…”

Antidepressant behavioral effects by dual inhibition of monoamine reuptake in the rat forced swimming test

“…An inhibitory serotonergic tone present in the locus ceruleus can alter NE discharge rate and the release of NE (Aston-Jones et al 1991), but with unpredictable reciprocal e¤ects on the release of 5-HT. Antidepressants with mixed e¤ects at NE and 5-HT reuptake, such as milnacipran, duloxetine and venlafaxine, have been shown to produce responses due to enhanced neurotransmission of both monoamine systems in vivo (Artigas 1995) and increase extracellular levels of both NE and 5-HT (Engleman et al 1995). Recent microdialysis studies have also shown that desipramine can alter extracellular levels of 5-HT (Chen and Reith 1994) or potentiate the e¤ects of ßuoxetine on extracellular 5-HT in the frontal cortex (Bel and Artigas 1996).…”

Comparative effects of duloxetine and desipramine on sleep EEG in healthy subjects

“…Duloxetine is a new antidepressant for which preclinical (Engleman et al 1995;Kihara and Ikeda 1995;Bymaster et al 2001) and clinical (Chalon et al 2004) data implicate inhibition of the reuptake transporters for both 5-HT and NE. Duloxetine has a half-life of 12.1 h, thus reaching steady state blood concentrations 2.5 days after the first dose (Sharma et al 2000), and has been administered to adult depressed patients at doses up to 120 mg/day.…”