Serotonin

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Ray W Fuller - One of the best experts on this subject based on the ideXlab platform.

  • Serotonin uptake inhibitors: Uses in clinical therapy and in laboratory research
    Progress in drug research, 1995
    Co-Authors: Ray W Fuller
    Abstract:

    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.

  • uptake inhibitors increase extracellular Serotonin concentration measured by brain microdialysis
    Life Sciences, 1994
    Co-Authors: Ray W Fuller
    Abstract:

    Abstract The physiological role of the Serotonin transporter on Serotonin neuronal membranes apparently is to inactivate Serotonin that has been released into the synaptic cleft. Drugs that inhibit the uptake of Serotonin increase the amount of Serotonin in the synaptic cleft and enhance serotonergic neurotransmission. As an adaptive response to the increased amount of Serotonin in the synaptic cleft, Serotonin neurons decrease their firing and release of Serotonin to limit the magnitude of the increase in extracellular Serotonin concentration. The increase in extracellular Serotonin in rat brain caused by inhibitors of the Serotonin uptake carrier has been characterized by brain microdialysis coupled to liquid chromatography with electrochemical detection. These drugs cause rapid accumulation of extracellular Serotonin in several brain regions, although the increase in frontal cortex may be smaller than in other nerve terminal regions or in the cell body-containing raphe region.

  • Serotonin uptake and Serotonin uptake inhibition
    Annals of the New York Academy of Sciences, 1990
    Co-Authors: Ray W Fuller, David T Wong
    Abstract:

    : 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.

Geoffrey K Isbister - One of the best experts on this subject based on the ideXlab platform.

  • Serotonin toxicity from antidepressant overdose and its association with the T102C polymorphism of the 5-HT_2A receptor
    The Pharmacogenomics Journal, 2014
    Co-Authors: J M Cooper, D A Newby, I M Whyte, G Carter, A L Jones, Geoffrey K Isbister
    Abstract:

    Serotonin toxicity results from Serotonin excess in the central nervous system from serotonergic drugs. Previous studies suggest an association between T102C polymorphism of the Serotonin 2A (5-hydroxytryptamine 2A) receptor gene and serotonergic adverse effects with serotonergic drugs. We aimed to determine whether there is an association between the T102C polymorphism and Serotonin toxicity in patients taking serotonergic drug overdoses. Ninety-five patients presenting with serotonergic drug overdoses were examined for Serotonin toxicity and had blood collected for DNA analysis. A diagnosis of Serotonin toxicity was made in 14 patients (15%) based on the Hunter Serotonin Toxicology Criteria. Four of the 14 patients (29%) with Serotonin toxicity had the C/C genotype compared with 20/81 (25%) without Serotonin toxicity. There were no differences in age or sex, but the median defined daily dose taken by patients with Serotonin toxicity was 27 (14–84) compared with 18 (2–136) in patients without Serotonin toxicity ( P =0.06). There was no association between Serotonin toxicity and the T102C polymorphism in patients taking a serotonergic drug overdose.

  • Serotonin toxicity a practical approach to diagnosis and treatment
    The Medical Journal of Australia, 2007
    Co-Authors: Geoffrey K Isbister, Nicholas A Buckley, Ian M Whyte
    Abstract:

    Serotonin toxicity results from an excess of Serotonin (5-hydroxytryptamine [5-HT]) in the central nervous system (CNS), which can be due to several different pharmacological mechanisms. These include inhibition of the metabolism of Serotonin (monoamine oxidase inhibitors), prevention of the reuptake of Serotonin in nerve terminals (Serotonin reuptake inhibitors), and increased Serotonin precursors (tryptophan) or Serotonin release (Serotonin-releasing agents) (Box 2). The resulting excess CNS Serotonin acts on Serotonin receptors and produces the clinical effects. The exact role of the various Serotonin receptors is not completely clear, but there is good evidence that the severe life-threatening clinical effects, such as rigidity and hyperthermia, are mediated by the 5-HT2A receptors. 1,5

  • the hunter Serotonin toxicity criteria simple and accurate diagnostic decision rules for Serotonin toxicity
    QJM: An International Journal of Medicine, 2003
    Co-Authors: E J C Dunkley, Geoffrey K Isbister, David Sibbritt, Andrew H Dawson, Ian M Whyte
    Abstract:

    Background:  There are difficulties with the diagnosis of Serotonin toxicity, particularly with the use of Sternbach’s criteria. Aim:  To improve the criteria for diagnosing clinically significant Serotonin toxicity. Design:  Retrospective analysis of prospectively collected data Methods: We studied all patients admitted to the Hunter Area Toxicology Service (HATS) following an overdose of a serotonergic drug from January 1987 to November 2002 ( n  = 2222). Main outcomes were: diagnosis of Serotonin toxicity by a clinical toxicologist, fulfilment of Sternbach’s criteria and treatment with a Serotonin receptor (5-HT2A) antagonist. A learning dataset of 473 selective Serotonin reuptake inhibitor (SSRI)-alone overdoses was used to determine individual clinical features predictive of Serotonin toxicity by univariate analysis. Decision rules using CART analysis were developed, and tested on the dataset of all serotonergic overdose admissions. Results:  Numerous clinical features were associated with Serotonin toxicity, but only clonus (inducible, spontaneous or ocular), agitation, diaphoresis, tremor and hyperreflexia were needed for accurate prediction of Serotonin toxicity as diagnosed by a clinical toxicologist. Although the learning dataset did not include patients with life-threatening Serotonin toxicity, hypertonicity and maximum temperature > 38°C were universal in such patients; these features were therefore added. Using these seven clinical features, decision rules (the Hunter Serotonin Toxicity Criteria) were developed. These new criteria were simpler, more sensitive (84% vs. 75%) and more specific (97% vs. 96%) than Sternbach’s criteria. Discussion:  These redefined criteria for Serotonin toxicity should be more sensitive to Serotonin toxicity and less likely to yield false positives.

Irwin Lucki - One of the best experts on this subject based on the ideXlab platform.

  • the spectrum of behaviors influenced by Serotonin
    Biological Psychiatry, 1998
    Co-Authors: Irwin Lucki
    Abstract:

    The diverse array of behavioral effects of Serotonin form the basis for understanding its potential role as an etiological marker in psychiatric disorders and for the successful pharmacologic intervention of drugs regulating Serotonin neurotransmission in behavior. General theories of the behavioral functions of Serotonin have implicated Serotonin as a general inhibitor of behavioral responding and in modulating motor behavior. The ability of Serotonin to regulate behavioral satiety and macronutrient selection provides the basis for pharmacologic treatment of obesity and eating disorders. The role of Serotonin in behavioral suppression may be important in social behavior involving aggression and anxiety. The role of Serotonin in neuroendocrine regulation provides a basis for understanding Serotonin dysregulation in depression. Animal behavior tests are being used to better understand the neural substrates underlying the behavioral effects of antidepressant drugs and to address important issues in clinical treatment. The integration of information between basic and clinical studies provides the basis for future development of more sophisticated pharmacologic treatments of psychiatric disorders.

  • The presence of a Serotonin uptake inhibitor alters pharmacological manipulations of Serotonin release
    Neuroscience, 1993
    Co-Authors: Deborah S. Kreiss, Scott Wieland, Irwin Lucki
    Abstract:

    The present study investigated the effects of the presence of the Serotonin uptake inhibitor citalopram in the perfusion medium on pharmacological manipulations which increased and decreased striatal Serotonin release using in vivo microdialysis. A high performance liquid chromatography detection system equipped with a microbore column was used which reduced the detection limit to 0.5 fmol Serotonin/5 μl sample and enabled basal striatal Serotonin release to be measured without the addition of a Serotonin uptake inhibitor to the perfusion medium. Although Serotonin uptake inhibitors have frequently been used to enhance the Serotonin content of dialysate samples, the effects of the presence of Serotonin uptake inhibitors on pharmacological manipulations which increased and decreased the release of Serotonin have not yet been characterized. Serotonin release was reduced by the systemic administration of the 5-HTIA receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Although 5-HT release was reduced by 8-OH-DPAT after the addition of citalopram, the 5-HTIA receptor agonist did not reduce absolute levels of extracellular Serotonin below basal values of Serotonin measured in the absence of citalopram. In addition, citalopram dramatically prevented the four-fold increase in the release of Serotonin produced by the systemic administration of the Serotonin-releasing agent fenfluramine. The blockade of fenfluramine's effects by citalopram supports the hypothesis that transport of fenfluramine into serotonergic neurons is necessary to increase Serotonin release. This study demonstrates that the use of an HPLC detection system equipped with a microbore column can reliably measure basal Serotonin release using in vivo microdialysis. Evaluation of the effects of the addition of citalopram to the perfusion medium suggests that the response to pharmacological manipulations of Serotonin release may be substantially altered by the presence of an uptake inhibitor.

David T Wong - One of the best experts on this subject based on the ideXlab platform.

  • Serotonin uptake and Serotonin uptake inhibition
    Annals of the New York Academy of Sciences, 1990
    Co-Authors: Ray W Fuller, David T Wong
    Abstract:

    : 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.

Ian M Whyte - One of the best experts on this subject based on the ideXlab platform.

  • Serotonin toxicity a practical approach to diagnosis and treatment
    The Medical Journal of Australia, 2007
    Co-Authors: Geoffrey K Isbister, Nicholas A Buckley, Ian M Whyte
    Abstract:

    Serotonin toxicity results from an excess of Serotonin (5-hydroxytryptamine [5-HT]) in the central nervous system (CNS), which can be due to several different pharmacological mechanisms. These include inhibition of the metabolism of Serotonin (monoamine oxidase inhibitors), prevention of the reuptake of Serotonin in nerve terminals (Serotonin reuptake inhibitors), and increased Serotonin precursors (tryptophan) or Serotonin release (Serotonin-releasing agents) (Box 2). The resulting excess CNS Serotonin acts on Serotonin receptors and produces the clinical effects. The exact role of the various Serotonin receptors is not completely clear, but there is good evidence that the severe life-threatening clinical effects, such as rigidity and hyperthermia, are mediated by the 5-HT2A receptors. 1,5

  • the hunter Serotonin toxicity criteria simple and accurate diagnostic decision rules for Serotonin toxicity
    QJM: An International Journal of Medicine, 2003
    Co-Authors: E J C Dunkley, Geoffrey K Isbister, David Sibbritt, Andrew H Dawson, Ian M Whyte
    Abstract:

    Background:  There are difficulties with the diagnosis of Serotonin toxicity, particularly with the use of Sternbach’s criteria. Aim:  To improve the criteria for diagnosing clinically significant Serotonin toxicity. Design:  Retrospective analysis of prospectively collected data Methods: We studied all patients admitted to the Hunter Area Toxicology Service (HATS) following an overdose of a serotonergic drug from January 1987 to November 2002 ( n  = 2222). Main outcomes were: diagnosis of Serotonin toxicity by a clinical toxicologist, fulfilment of Sternbach’s criteria and treatment with a Serotonin receptor (5-HT2A) antagonist. A learning dataset of 473 selective Serotonin reuptake inhibitor (SSRI)-alone overdoses was used to determine individual clinical features predictive of Serotonin toxicity by univariate analysis. Decision rules using CART analysis were developed, and tested on the dataset of all serotonergic overdose admissions. Results:  Numerous clinical features were associated with Serotonin toxicity, but only clonus (inducible, spontaneous or ocular), agitation, diaphoresis, tremor and hyperreflexia were needed for accurate prediction of Serotonin toxicity as diagnosed by a clinical toxicologist. Although the learning dataset did not include patients with life-threatening Serotonin toxicity, hypertonicity and maximum temperature > 38°C were universal in such patients; these features were therefore added. Using these seven clinical features, decision rules (the Hunter Serotonin Toxicity Criteria) were developed. These new criteria were simpler, more sensitive (84% vs. 75%) and more specific (97% vs. 96%) than Sternbach’s criteria. Discussion:  These redefined criteria for Serotonin toxicity should be more sensitive to Serotonin toxicity and less likely to yield false positives.