Corpus ID: 25835708

Effects of duloxetine, an antidepressant drug candidate, on concentrations of monoamines and their metabolites in rats and mice.

  title={Effects of duloxetine, an antidepressant drug candidate, on concentrations of monoamines and their metabolites in rats and mice.},
  author={Ray W. Fuller and Susan K. Hemrick-Luecke and Harold D. Snoddy},
  journal={The Journal of pharmacology and experimental therapeutics},
  volume={269 1},
Duloxetine, (+)-N-methyl-3-(1-naphthalenyloxy)-2-thiophenepropanamine, is an inhibitor of the serotonin and norepinephrine neuronal transporters (Wong et al., 1993). In mice, duloxetine antagonized the depletion of brain serotonin by p-chloroamphetamine (ED50 = 2.5 mg/kg, i.p.) and the depletion of heart norepinephrine by 6-hydroxydopamine (ED50 = 1.1 mg/kg, i.p.). Brain concentrations of 5-hydroxyindoleacetic acid were decreased by duloxetine at 2 hr after doses of 1, 3 and 10 mg/kg and at 1… Expand
Duloxetine (LY 248686): an inhibitor of serotonin and noradrenaline uptake and an antidepressant drug candidate.
  • D. Wong
  • Chemistry, Medicine
  • Expert opinion on investigational drugs
  • 1998
In preliminary clinical trials, duloxetine has shown antidepressive effects in patients with major depression and offers an opportunity to utilise combined central 5-HT and NE neuronal pathways to improve the treatment of patients withmajor depression. Expand
Simultaneous Increases of Extracellular Monoamines in Microdialysates from Hypothalamus of Conscious Rats by Duloxetine, a Dual Serotonin and Norepinephrine Uptake Inhibitor
The ability to produce robust increases of extracellular 5-HT and NE levels suggests that duloxetine may potentially be a highly effective antidepressant agent. Expand
Effect of long-term administration of duloxetine on the function of serotonin and noradrenaline terminals in the rat brain
The data suggest that long-term administration of duloxetine is able to induce changes in the 5-HT and NA systems that lead to enhanced release of both 5-hydroxytryptamine and NA in some limbic brain areas, and may be a useful antidepressant compound. Expand
Effects of Duloxetine on Norepinephrine and Serotonin Transporter Activity in Healthy Subjects
Duloxetine significantly affected 5-HT and NE turnover in the central nervous system and periphery; these effects presumably occurred via inhibition of reuptake by the 5- HTT and NET, as indicated by effects on functional reuptakes inhibition ex vivo. Expand
Comparative Affinity of Duloxetine and Venlafaxine for Serotonin and Norepinephrine Transporters in vitro and in vivo, Human Serotonin Receptor Subtypes, and Other Neuronal Receptors
Duloxetine more potently blocks 5-HT and NE transporters in vitro and in vivo than venlafaxine. Expand
The selective norepinephrine reuptake inhibitor, LY368975, reduces food consumption in animal models of feeding.
LY368975 is an orally available and centrally active NE reuptake inhibitor that is capable of reducing food consumption in rodents and may have use in the treatment of obesity and eating disorders. Expand
Electrophysiological effects of fluoxetine and duloxetine in the dorsal raphe nucleus and hippocampus.
Co-application of fluoxetine with 5-HT at the same iontophoretic currents significantly increased the RT50 values produced by 5- HT application alone, contributing to understanding the cellular mechanisms of these agents which may be useful in the treatment of depression. Expand
Antagonism of Serotonin 5‐HT1A Receptors Potentiates the Increases in Extracellular Monoamines Induced by Duloxetine in Rat Hypothalamus
It is demonstrated that antagonism of somatodendritic 5‐HT1A autoreceptors and concomitant inhibition of 5‐ HT and NE uptake with duloxetine may promote synergistic increases in levels of extracellular 5-HT, NE, and DA in hypothalamus of conscious, freely moving rats. Expand
Assessment of the Serotonin and Norepinephrine Reuptake Blocking Properties of Duloxetine in Healthy Subjects
Both duloxetine, at doses of 20 to 60 mg/day, and clomipramine significantly interfered with the 5-HT reuptake process, as demonstrated by marked decreases in blood 4-HT concentrations, and it is possible that the highest dose of dulOxetine represents the threshold regimen for NE reuptakes inhibition. Expand
Clinical Assessment of Norepinephrine Transporter Blockade Through Biochemical and Pharmacological Profiles
The findings suggest that the degree of NET blockade can be assessed with the plasma or urine DHPG/NE ratio and the pressor effect of tyramine, whereas tyramines exhibits a linear relation, with NET inhibition commencing at a higher dose. Expand


LY248686, A New Inhibitor of Serotonin and Norepinephrine Uptake
LY248686 has a favorable pharmacological profile as a potential antidepressant drug because of its lack of affinity for receptors of 5-HT, NE, DA, acetylcholine, histamine and naloxone, and its ability to inhibit 5- HT and NE uptake simultaneously. Expand
Pharmacological interference with the neurotoxic action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in the mouse.
The results suggest that MAO-B and the catecholamine uptake system may be critically involved at certain steps in the neurotoxic action of MPTP on catechlamine neurons. Expand
Inhibition of serotonin reuptake.
Through the use of fluoxetine and other serotonin uptake inhibitors, the role of serotonin neurons in various brain functions--behavior, sleep, regulation of pituitary hormone release, thermoregulation, pain responsiveness, and so on--can be studied. Expand
MPTP: A Parkinsonism-causing Neurotoxic Substance
The past six years have witnessed an intense research effort centred around MPTP, l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine, a compound resembling meperidine chemically and pharmacologically but chemically distinct from drugs that are controlled substances. Expand
Pharmacology of brain epinephrine neurons.
  • R. Fuller
  • Biology, Medicine
  • Annual review of pharmacology and toxicology
  • 1982
The continued study of drugs affecting epinephrine neurons should be useful in elucidating functions of these neurons, which may be of use in the treatment of hypertension, psychiatric disorders, neuroendocrine dysfunction, and possibly other diseases. Expand