The Experts below are selected from a list of 126 Experts worldwide ranked by ideXlab platform
David T Wong - One of the best experts on this subject based on the ideXlab platform.
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fluoxetine a selective inhibitor of Serotonin Uptake
Medicinal Research Reviews, 1991Co-Authors: Ray W Fuller, David T Wong, David W RobertsonAbstract:: In summary, fluoxetine is a highly selective Serotonin Uptake inhibitor in vitro and in vivo. The conformation of fluoxetine, which resembles that of sertraline and other Serotonin Uptake inhibitors, appears to be a key feature that enables its high affinity and selective interaction with the Serotonin transporter. The para-trifluoromethyl substituent, however, is also a pivotal structural element. The molecular pharmacology of fluoxetine has been well-defined, and its in vivo pharmacological effects appear to be mediated almost exclusively by Serotonin Uptake inhibition. Its selectivity for the Serotonin transporter, lack of affinity for neurotransmitter receptors, and retention of selectivity following metabolism to norfluoxetine make fluoxetine a useful tool to explore pharmacologically induced increases in Serotonin neurotransmission. Fluoxetine has found a variety of therapeutic application. Its use in treating depression has been most extensively studied, but controlled clinical studies also suggest the drug may have a role in treating obesity and bulimia. Moreover, a variety of other psychiatric disorders may be treatable with this drug. Regardless of the outcome of these clinical trials, it is apparent that fluoxetine has found a useful niche in therapy, and can be used as a probe to determine the role of Serotonin in modulating human pathophysiologies.
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Serotonin Uptake and Serotonin Uptake inhibition
Annals of the New York Academy of Sciences, 1990Co-Authors: Ray W Fuller, David T WongAbstract:: Serotonin Uptake carriers occur on Serotonin neurons, on glial cells and on blood platelets. The Uptake carrier on Serotonin neurons inactivates Serotonin that has been released into the synaptic cleft by transporting it back into the nerve terminal. The Serotonin Uptake carrier is the means by which blood platelets acquire Serotonin, since they do not synthesize it. The function of the Serotonin Uptake carrier on glial cells is poorly understood. Selective inhibitors of Serotonin Uptake enhance neurotransmission via serotonergic neurons and have been useful pharmacologic tools for studying physiologic roles of Serotonin neurons. Some Serotonin Uptake inhibitors are finding therapeutic uses in mental depression and other psychiatric disorders and in treating obesity and bulimia; other therapeutic applications continue to be evaluated.
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Fluoxetine and its two enantiomers as selective Serotonin Uptake inhibitors.
Acta pharmaceutica nordica, 1990Co-Authors: David T Wong, Fuller Rw, Robertson DwAbstract:Abstract The biochemical and pharmacological profiles of R,S-fluoxetine and its R and S enantiomers have been compared and reviewed. Both enantiomers exhibit profiles analogous to R,S-fluoxetine as inhibitors of Serotonin Uptake in vitro and in vivo with about equal potencies or a eudismic ratio near unity.
Meir Shinitzky - One of the best experts on this subject based on the ideXlab platform.
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correlation between cortisol level and Serotonin Uptake in patients with chronic stress and depression
Cognitive Affective & Behavioral Neuroscience, 2001Co-Authors: Gustavo E Tafet, Victor P Idoyagavargas, Denise P Abulafia, Jorgelina M Calandria, Silvia S Roffman, Amabella Chiovetta, Meir ShinitzkyAbstract:In a recent study (Tafet, Toister-Achituv, & Shinitzky, 2001), we demonstrated that cortisol induces an increase in the expression of the gene coding for the Serotonin transporter, associated with a subsequent elevation in the Uptake of Serotonin. This stimulatory effect, produced upon incubation with cortisol in vitro, was observed in peripheral blood lymphocytes from normal subjects. In the present work we investigated the cortisol-induced increase in Serotonin Uptake in lymphocytes from hypercortisolemic patients, including subjects with major depressive disorder (n = 8), and subjects with generalized anxiety disorder (n = 12), in comparison with a control group of normal healthy subjects (n = 8). A significant increase in Serotonin Uptake (+37%+14, M + SD) was observed in the control group, whereas neither the generalized anxiety disorder nor the major depression group exhibited changes in Serotonin Uptake upon incubation with cortisol. It is likely that under chronic stress or depression, the capacity for increase in Serotonin transporter has reached its limit due to the chronically elevated blood cortisol level. The physiological and diagnostic implications of this observation are discussed.
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Enhancement of Serotonin Uptake by cortisol: A possible link between stress and depression
Cognitive Affective & Behavioral Neuroscience, 2001Co-Authors: Gustavo E Tafet, Mira Toister-achituv, Meir ShinitzkyAbstract:Stress and depression are characterized by elevation of circulating cortisol, as well as by changes in physiological functions. In this study, we addressed the possibility that elevated cortisol is also associated with the origin and development of depression. We report here that cortisol at the nM-μM concentration range induces a substantial increase in Serotonin Uptake both in vitro, by human peripheral blood lymphocytes (PBLs) and cortical neuronal cells, and in vivo, by rabbit PBLs, owing to promotion of synthesis of the Serotonin transporter. These findings offer a novel molecular mechanism for depression associated with stress. Accordingly, the elevated cortisol induced by stress increases Serotonin Uptake, under both rest and nerve stimulation, which is overtly expressed in symptoms of depression.
Joel E Kleinman - One of the best experts on this subject based on the ideXlab platform.
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Serotonin Uptake sites and Serotonin receptors are altered in the limbic system of schizophrenics
Neuropsychopharmacology, 1993Co-Authors: Jeffrey N Joyce, Audi Shane, Nedra Lexow, Andrew Winokur, Manuel F Casanova, Joel E KleinmanAbstract:Serotonin Uptake Sites and Serotonin Receptors Are Altered in the Limbic System of Schizophrenics
Ray W Fuller - One of the best experts on this subject based on the ideXlab platform.
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Serotonin Uptake inhibitors: Uses in clinical therapy and in laboratory research
Progress in drug research, 1995Co-Authors: Ray W FullerAbstract:Shortly after Serotonin was discovered to be present in the brain in 1953, it was suspected to be a neurotransmitter there. Just over 40 years later, much has been learned about brain Serotonin neurons and their physiological roles. One contributor to this advance in knowledge has been a group of compounds that selectively inhibit Serotonin Uptake. The study of these compounds in laboratory animals has not only given insight into the operation of Serotonin neurons themselves and how the synthesis and release of Serotonin is controlled, but also has helped in the understanding of physiological roles of Serotonin neurons. Moreover, these Serotonin Uptake inhibitors have been therapeutically useful in treating mental depression, bulimia and obsessive-compulsive disorder in humans, and there is some indication they may have therapeutic effects in a variety of other diseases. The continued study of these compounds will further increase our knowledge about the role of Serotonin in disease and may lead to ways of enhancing their therapeutic effects.
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Role of norfluoxetine in the inhibition of desipramine metabolism and in the inhibition of Serotonin Uptake after fluoxetine administration to rats.
Research communications in chemical pathology and pharmacology, 1991Co-Authors: Ray W Fuller, Snoddy HdAbstract:: Fluoxetine, a Serotonin Uptake inhibitor, is known to inhibit the metabolism of some drugs including desipramine, resulting in increased brain and blood levels of desipramine when the drugs are co-administered to rats. Norfluoxetine, the N-desmethyl metabolite of fluoxetine, was found to be less potent than fluoxetine in increasing brain and blood levels of desipramine in rats. Norfluoxetine was essentially equipotent to fluoxetine in decreasing brain concentrations of 5-hydroxyindoleacetic acid (5-HIAA) as a consequence of Serotonin Uptake inhibition. After the injection of fluoxetine into rats, brain levels of fluoxetine predominated over those of norfluoxetine at 1 hour, but at longer times (out to 24 hours), norfluoxetine levels were higher in brain (and in liver) than fluoxetine levels. Brain levels of 5-HIAA were decreased for at least 24 hours after fluoxetine injection, due apparently to the persistence of and inhibition of Serotonin Uptake by norfluoxetine. When desipramine was injected 16 hrs after fluoxetine injection, brain levels of desipramine were no longer elevated. The results suggest that norfluoxetine contributes in a major way to the inhibition of Serotonin Uptake after fluoxetine administration but contributes less, if at all, to the inhibition of desipramine metabolism.
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fluoxetine a selective inhibitor of Serotonin Uptake
Medicinal Research Reviews, 1991Co-Authors: Ray W Fuller, David T Wong, David W RobertsonAbstract:: In summary, fluoxetine is a highly selective Serotonin Uptake inhibitor in vitro and in vivo. The conformation of fluoxetine, which resembles that of sertraline and other Serotonin Uptake inhibitors, appears to be a key feature that enables its high affinity and selective interaction with the Serotonin transporter. The para-trifluoromethyl substituent, however, is also a pivotal structural element. The molecular pharmacology of fluoxetine has been well-defined, and its in vivo pharmacological effects appear to be mediated almost exclusively by Serotonin Uptake inhibition. Its selectivity for the Serotonin transporter, lack of affinity for neurotransmitter receptors, and retention of selectivity following metabolism to norfluoxetine make fluoxetine a useful tool to explore pharmacologically induced increases in Serotonin neurotransmission. Fluoxetine has found a variety of therapeutic application. Its use in treating depression has been most extensively studied, but controlled clinical studies also suggest the drug may have a role in treating obesity and bulimia. Moreover, a variety of other psychiatric disorders may be treatable with this drug. Regardless of the outcome of these clinical trials, it is apparent that fluoxetine has found a useful niche in therapy, and can be used as a probe to determine the role of Serotonin in modulating human pathophysiologies.
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Serotonin Uptake and Serotonin Uptake inhibition
Annals of the New York Academy of Sciences, 1990Co-Authors: Ray W Fuller, David T WongAbstract:: Serotonin Uptake carriers occur on Serotonin neurons, on glial cells and on blood platelets. The Uptake carrier on Serotonin neurons inactivates Serotonin that has been released into the synaptic cleft by transporting it back into the nerve terminal. The Serotonin Uptake carrier is the means by which blood platelets acquire Serotonin, since they do not synthesize it. The function of the Serotonin Uptake carrier on glial cells is poorly understood. Selective inhibitors of Serotonin Uptake enhance neurotransmission via serotonergic neurons and have been useful pharmacologic tools for studying physiologic roles of Serotonin neurons. Some Serotonin Uptake inhibitors are finding therapeutic uses in mental depression and other psychiatric disorders and in treating obesity and bulimia; other therapeutic applications continue to be evaluated.
David W Robertson - One of the best experts on this subject based on the ideXlab platform.
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fluoxetine a selective inhibitor of Serotonin Uptake
Medicinal Research Reviews, 1991Co-Authors: Ray W Fuller, David T Wong, David W RobertsonAbstract:: In summary, fluoxetine is a highly selective Serotonin Uptake inhibitor in vitro and in vivo. The conformation of fluoxetine, which resembles that of sertraline and other Serotonin Uptake inhibitors, appears to be a key feature that enables its high affinity and selective interaction with the Serotonin transporter. The para-trifluoromethyl substituent, however, is also a pivotal structural element. The molecular pharmacology of fluoxetine has been well-defined, and its in vivo pharmacological effects appear to be mediated almost exclusively by Serotonin Uptake inhibition. Its selectivity for the Serotonin transporter, lack of affinity for neurotransmitter receptors, and retention of selectivity following metabolism to norfluoxetine make fluoxetine a useful tool to explore pharmacologically induced increases in Serotonin neurotransmission. Fluoxetine has found a variety of therapeutic application. Its use in treating depression has been most extensively studied, but controlled clinical studies also suggest the drug may have a role in treating obesity and bulimia. Moreover, a variety of other psychiatric disorders may be treatable with this drug. Regardless of the outcome of these clinical trials, it is apparent that fluoxetine has found a useful niche in therapy, and can be used as a probe to determine the role of Serotonin in modulating human pathophysiologies.
