Fluoxetine: Pharmacology, Mechanisms of Action and Potential Side Effects

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Graziano Pinna, PhD (Editor)
University of Illinois at Chicago, Psychiatric Institute, Chicago, Illinois, USA

Series: Pharmacology – Research, Safety Testing and Regulation
BISAC: MED071000

Fluoxetine, best known by the trade name Prozac®, unlike other psychotropic drugs whose effects were serendipitously stumbled upon, was the first developed for a precise mechanism of action, that is, the ability to selectively inhibit serotonin reuptake, based upon the theory that increasing the availability of serotonin would treat major depression. Once approved by the FDA in 1987, fluoxetine quickly became the most prescribed psychotropic drug worldwide and its success in improving mood disorders has triggered the development of a large number of congener molecules, commonly known as SSRIs after their purported mechanism of action.

However, a quarter of a century after its development, the idea that fluoxetine asserts its positive behavioral effect through inhibition of serotonergic reuptake is not firmly established. This book reviews several preclinical and clinical reports suggesting that the pharmacological effects of fluoxetine may be mediated by means other than the regulation of serotonin, including the regulation of gene expression, modifying epigenetic mechanisms as well as modifying microRNAs. One of the most prominent mechanisms for the therapeutic relevance of fluoxetine relates to influencing neuroplasticity by enhacing neurotropic factors, including BDNF signaling and altering adult neurogenesis. The ability of fluoxetine to rapidly increase neurosteroid levels accounts for the fast anxiolytic effects of this drug. Fluoxetine action at sigma-1 receptor or modulating glutamatergic neurotransmission as well as the combination of fluoxetine with other psychotropic drugs is discussed in relation to its therapeutic effects.

While fluoxetine was primarily prescribed as an antidepressant, this drug currently represents a treatment of choice for a broad spectrum of psychiatric disorders, including post-traumatic stress disorder and a range of anxiety disorders. This drug even possesses analgesic actions and is a valuable therapy for stroke. This book also highlights emerging evidence on the gender-specific effects of fluoxetine, its potential adverse features, including its addiction liability in combination with psychostimulants, and the impact of perinatal fluoxetine exposure. (Imprint: Nova Biomedical)

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Table of Contents

Preface

Chapter 1 – Activity of Fluoxetine in Animal Models of Depression and Anxiety (pp. 1-24)
Trevor R. Norman (Department of Psychiatry, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia)

Chapter 2 – The Neurosteroidogenic Action of Fluoxetine Unveils the Mechanism for the Anxiolytic Property of SSRIs (pp. 25-42)
Graziano Pinna (The Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA)

Chapter 3 – Developmental Fluoxetine Exposure and Neuroendocrine Outcomes (pp. 43-70)
Jodi L. Pawluski, Mary Gemmel, Eszter Császár, Harry W. M. Steinbusch and Ine Rayen (School for Mental Health and Neuroscience, Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands, and others)

Chapter 4 – The Impact of Fluoxetine Treatment on BDNF Signaling and Cellular Plasticity in the Brain (pp. 71-96)
Jochen De Vry, Fabien Boulle, Bart P. F. Rutten, Daniel L. A. van den Hove and Jos Prickaerts (Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands, European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, the Netherlands)

Chapter 5 – Fluoxetine and Its Novel Effect on Adult Neurogenesis (pp. 97-106)
Koji Ohira (Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan)

Chapter 6 – The Role of Neurotrophins in Fluoxetine‘s Mechanism of Action (pp. 107-124)
Maria Ladea and Mihai Bran (University of Medicine and Pharmacy “Carol Davila”, Bucharest; Clinical Hospital of Psychiatry “Prof. Dr. Alexandru Obregia”, Bucharest, Romania, Coltea Hospital, Bucharest, Romania)

Chapter 7 – The Role of Epigenetic Mechanisms in the Therapeutic Effects of Fluoxetine and Other Selective Serotonin Reuptake Inhibitors (pp. 125-146)
Kristen Ashley Horner (Mercer University School of Medicine, Macon, GA, USA)

Chapter 8 – microRNAs As Novel Players in Depression Pathogenesis and in the Mechanisms of Action of Fluoxetine and Other Antidepressants (pp. 147-166)
Guangxing Bai, Michael Dunbar, Levi D. Miller, Bhaskar Roy, Ian J. Soller, Richard C. Shelton and Yogesh Dwivedi (Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA)
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Chapter 9 – Preclinical and Clinical Aspects of a Combination Therapy with Antagonists to N-Methyl-D-Aspartate Receptor to Enhance Fluoxetine‘s Antidepressant Effects (pp. 167-186)
Gislaine Z. Réus, Helena M. Abelaira, Fabricia Petronilho and João Quevedo (Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA, and others)

Chapter 10 – Fluoxetine and Glutamate Release and Transmission (pp. 187-206)
Laura Musazzi, Paolo Tornese, Giulia Treccani and Maurizio Popoli (Laboratory of Neuropsychopharmacology and Functional Neurogenomics – Dipartimento di Scienze Farmacologiche e Biomolecolari and CEND, Università degli Studi di Milano, Milano, Italy)

Chapter 11 – Fluoxetine and Other SSRI Antidepressants Potentiate Addiction-Related Gene Regulation by Psychostimulant Medications (pp. 207-226)
Vincent Van Waes and Heinz Steiner (Department of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA, and others)

Chapter 12 – Role of Fluoxetine on Depression-Related Pathophysiological Mechanisms (pp. 227-278)
Miroslav Adzic, Milos Mitic, Iva Lukic, Jelena Djordjevic and Marija B. Radojcic (Department of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, University of Belgrade, Serbia)

Chapter 13 – Clinical Implications of Fluvoxamine and Fluoxetine with Sigma-1 Receptor Chaperone Activity in the Treatment of Neuropsychiatric Disorders (pp. 279-294)
Yakup Albayrak and Kenji Hashimoto (Namýk Kemal University, Medical Faculty, Department of Psychiatry, Tekirdag, Turkey)

Chapter 14 – Fluoxetine: Pharmacological Analysis of Depression-Like Responses in Zebrafish (pp. 295-306)
Julian Pittman, Roaa Hadi and Katie Ichikawa (Department of Biological & Environmental Sciences, Troy University, Troy, AL, USA)

Chapter 15 – How Could Fluoxetine Exert Therapeutic Effects in Stroke? (pp. 307-328)
Virginie Beray-Berthat, Michel Plotkine and Raymond Mongeau (Pharmacologie de la circulation cérébrale, Université Paris Descartes, Paris, France)

Index


Reviews

Click here, to read the review by – Dr. Thelma Lovick, BSc(Manch), Phd(Birm), Reader, Honorary Reader, School of Physiology and Pharmacology, University of Bristol.


It is with great honor that we would like to announce that Dr. Graziano Pinna has been nominated for the prestigious Sardus Pater Award for his discovery in the field of depression, anxiety, and PTSD.

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