The Search for Antidepressants - An Integrative View of Drug Discovery

Book Series: Frontiers in Drug Discovery

Volume 2

by

Andre F. Carvalho, Gislaine Zilli Reus, João Luciano de Quevedo

DOI: 10.2174/97816810847321170201
eISBN: 978-1-68108-473-2, 2017
ISBN: 978-1-68108-474-9
ISSN: 2542-7350 (Print)
ISSN: 2214-6210 (Online)



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Major depressive disorder (MDD) is a prevalent, chronic, and recurring mental disorder. This disorder is a leading source of disabi...[view complete introduction]

Table of Contents

The Search For Novel Antidepressants

- Pp. i

Andre F. Carvalho, Gislaine Z. Réus and João Quevedo

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Preface

- Pp. ii

Andre F. Carvalho, Gislaine Z. Réus and João Quevedo

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List of Contributors

- Pp. iii-iv (2)

Andre F. Carvalho, Gislaine Z. Reus and João Quevedo

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Innovative Solutions to the Development of Novel Antidepressants

- Pp. 1-40 (40)

Daniela Felice, Alain M. Gardier, Connie Sanchez and Denis J. David

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Animal Models of Depression: Current Status and Perspectives

- Pp. 41-76 (36)

Morgana Moretti, Manuela P. Kaster and Ana Lúcia S. Rodrigues

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Potential Role of Optogenetics for The Development of Novel Antidepressants

- Pp. 77-98 (22)

T. Chase Francis and Mary Kay Lobo

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The Relevance of Studies in Healthy Human Volunteers for The Development of Novel Antidepressants: Exploring Endophenotypes

- Pp. 99-125 (27)

Renato T. Ramos

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Monoamine Oxidase-A: A Valid Target for the Management of Depression

- Pp. 126-134 (9)

Bijo Mathew and Jerad Suresh

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Repurposed Drugs: A Shortcut to the Discovery of Novel Antidepressants?

- Pp. 135-176 (42)

Young Sup Woo, Yena Lee and Roger S. McIntyre

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Ketamine and Glutamatergic Compounds: Exploring Biomarkers and Mechanisms Related to Rapid Antidepressant Action

- Pp. 177-200 (24)

Gislaine Z. Réus, Helena M. Abelaira, Gerard Sanacora and João Quevedo

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Novel Antidepressant Targets for Cognitive Dysfunction in Major Depressive Disorder

- Pp. 201-221 (21)

Beatrice Bortolato and Andre F. Carvalho

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Oxidative and Nitrosative Stress, Immune Inflammation and Trptophan Catabolites in Driving Melatonergic Pathway Alterations in Depression: Treatment Implications

- Pp. 222-241 (20)

George Anderson and Michael Maes

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Novel Non-Monoaminergic Antidepressants: Focus on Neuropeptides

- Pp. 242-255 (14)

Donatella Marazziti, Federico Mucci, Stefano Baroni and Liliana Dell`Osso

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Novel Antidepressant Drugs: Exploring Neurotrophins and Intracellular Signaling Pathways

- Pp. 256-297 (42)

Gianluca Serafini, Admena Rreshketa, Maurizio Pompili, Paolo Girardi, Goutam Brahmachari and Mario Amore

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Shared Pathophysiology between Depression, Obesity and Metabolic Disturbances: Novel Antidepressant Targets?

- Pp. 298-356 (59)

Léa Décarie-Spain, Dominique Matthys and Stephanie E. Fulton

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The Development of Novel Antidepressants: Focus on Plant-based Drugs

- Pp. 357-390 (34)

Abir T. El-Alfy

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Subject Index

- Pp. 391-399 (9)

Andre F. Carvalho, Gislaine Z. Reus and João Quevedo

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Foreword

In spite of the undeniable progress of Psychiatry over the past 60 years, and hundreds of new molecules having been tested for the treatment of mental disorders, the pharmacological treatment of depression is far from being satisfactory. In the last decades, no significant paradigm shifts in the psychopharmacology of mood disorders have occurred, mostly because the development of novel antidepressant agents is limited by our limited understanding of the pathophysiology of the illness. In this context, Andre F. Carvalho, Gislaine Z. Reus, and João Quevedo have devoted their talent and effort to provide us with a crisp summary of the past, present, and future treatment options for the management of depression that will please both preclinical and clinical investigators in neuropsychopharmacology. This e-jewell, rather than e-book, (and its printed version) gathers prominent researchers in basic and clinical psychopharmacology, authoring thoughtful chapters on exciting topics such as animal models, optogenetics, endophenotypes, repurposing, cognitive dysfunction, biomarkers, oxidative stress, and the microbiota-brain axis, which are outstandingly relevant for understanding the current approach to the pathopshysiology of mood disorders. Modern and traditional treatment targets, such as glutamate receptors, monoamine-oxidase-A, intracellular signaling pathways, and new avenues based on the comorbidity between depression and metabolic syndrome, neuropeptides, or herbal remedies are also part of this comprehensive text which starts with a wonderful chapter on innovative solutions for the development of new antidepressant drugs. I personally enjoyed reading it and learnt much from it. In difficult times such as ours, when social and methodological hurdles are challenging our ability to translate scientific progress into true impactful innovation in this field, the reading of this book fuels fresh air into the community of scientists, clinicians, and perhaps informed patients who await answers or at least better questions for the understanding and management of depression.

Eduard Vieta, MD, PhD
Chair
Department of Psychiatry and Psychology, Hospital Clinic,
Institute of Neuroscience, University of Barcelona,
IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain


Preface

This eBook was conceived after an invitation by the Bentham Science Publishers due to the necessity to review novel antidepressant alternatives.

The prevalence of people with major depressive disorder (MDD) has increased drastically worldwide. In addition, many patients do not respond to classic antidepressant treatments. However, in the last years, new strategies have been studied in experimental and clinical approaches.

The development of novel treatment of MDD would decrease the morbidity and mortality, and consequently the economic burden associated with hospital. Some of these new treatment alternatives are associated with a fast antidepressant effects and low side effects compared to classical treatments. Several studies indicate that pathological mechanisms involved with MDD development are not only based on monoaminergic system, but also with metabolic disturbances, inflammation and a decrease in protein involved with neuroplasticity.

This eBook aims to contribute to an integrated understanding concerning innovative alternatives to treat MDD. It is based on cutting edge research and the outcome will shed light on the most appropriate approach to treat resistant-treatment MDD patients. It gathers a wide range of topics on the subject and includes several chapters with original material.

Authors and co-authors represent a multidisciplinary team that includes scientists and professors with a vast experience in the area, from different universities and research institutions. It is an attempt to encourage the implementation of alternative approaches to the classic antidepressants for humans.

The eBook is organized in fourteen chapters: the general introduction is followed by a review devoted to experimental models, optogenetics therapy, the role of healthy human volunteers, monoamine oxidase-A, repurposed drugs, glutamatergic compounds, cognition, oxidative and nitrosative stress, melatoninergic pathway, neuropeptides, gut microbiota, metabolic disturbances, and plant-based drugs.

Ultimately, we would like to thank all authors that have actively contributed to this eBook, and all people that someway helped us to bring it to daylight, including our family, friends, students and colleagues.

Andre F. Carvalho
Associate Professor of Psychiatry
Head, Translational Psychiatry Research Group
Faculty of Medicine
Federal University of Ceara
Fortaleza, CE
Brazil


Gislaine Zilli Reus
Laboratory of Neurosciences
University of Southern Santa Catarina
1105 - Av Universitaria
Brazil


João Luciano de Quevedo
Center for Translational Psychiatry
Department of Psychiatry and Behavioral Sciences
Medical School, The University of Texas Health Science Center at Houston
Houston, TX
USA

List of Contributors

Editor(s):
Andre F. Carvalho
Associate Professor of Psychiatry
Head, Translational Psychiatry Research Group
Faculty of Medicine
Federal University of Ceara
Fortaleza, CE
Brazil


Gislaine Zilli Reus
Laboratory of Neurosciences
University of Southern Santa Catarina
1105 - Av Universitaria
Brazil


João Luciano de Quevedo
Center for Translational Psychiatry
Department of Psychiatry and Behavioral Sciences
Medical School, The University of Texas Health Science Center at Houston
Houston, TX
USA




Contributor(s):
Abir T. El-Alfy
Department of Pharmaceutical Sciences,
College of Pharmacy, Chicago State University,
Chicago, IL,
USA


Admena Rreshketa
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry
University of Genoa
Italy


Alain M. Gardier
Institut National de la Santé et de la recherche Médicale UMR-S 1178 Santé Mentale et Santé Publique, Univ. Paris-Sud, Fac Pharmacie, Université Paris Saclay
Châtenay-Malabry
France


Ana Lúcia S. Rodrigues
Department of Biochemistry, Center of Biological Sciences
Universidade Federal de Santa Catarina, Campus Universitário, Florianópolis, SC
Brazil


Andre F. Carvalho
Department of Clinical Medicine and Psychiatry Research Group
Faculty of Medicine, Federal University of Ceara, Fortaleza, CE
Brazil


Beatrice Bortolato
Department of Mental Health, ULSS 10 “Veneto Orientale”
Venice
Italy


Bijo Mathew
Department of Pharmaceutical Chemistry, Ahalia School of Pharmacy
Division of Drug Design and Medicinal Chemistry Research Lab
Palakkad, Kerala
India


Connie Sanchez
Lundbeck Research USA, Inc., 215 College Road, 07652 Paramus, NJ
United States


Daniela Felice
Univ. Paris-Sud, Fac Pharmacie, Université Paris Saclay
Institut National de la Santé et de la recherche Médicale UMR-S 1178 Santé Mentale et Santé Publique
Châtenay-Malabry
France


Denis J. David
Univ. Paris-Sud, Fac Pharmacie, Université Paris Saclay
Institut National de la Santé et de la recherche Médicale UMR-S 1178 Santé Mentale et Santé Publique
Châtenay-Malabry
France


Dominique Matthys
University of Montreal Hospital Research Center (CRCHUM); Departments of Nutrition; Neuroscience
University of Montreal



Donatella Marazziti
Dipartimento di Medicina Clinica e Sperimentale, Section of Psychiatry
University of Pisa
Pisa
Italy


Federico Mucci
Dipartimento di Medicina Clinica e Sperimentale, Section of Psychiatry
University of Pisa
Pisa
Italy


George Anderson
CRC Scotland & London, Eccleston Square
London
UK


Gerard Sanacora
Yale University School of Medicine
New Haven, CT
USA


Gianluca Serafini
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry
University of Genoa
Italy


Gislaine Z. Réus
Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit
University of Southern Santa Catarina
Criciúma, SC
Brazil


Goutam Brahmachari
Department of Chemistry, Visva-Bharati University Santiniketan-731 235
Laboratory of Natural Products & Organic Synthesis
West Bengal
India


Helena M. Abelaira
Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina
Criciúma, SC
Brazil


Jane A. Foster
Department of Psychiatry & Behavioural Neurosciences @ St. Joseph's Healthcare
Hamilton


Jerad Suresh
Department of Pharmaceutical Chemistry, College of Pharmacy, Madras Medical College
Chennai
India


João Quevedo
Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit
University of Southern Santa Catarina
Criciúma, SC
Brazil


Léa Décarie-Spain
University of Montreal Hospital Research Center (CRCHUM); Departments of Nutrition; Neuroscience
University of Montreal



Liliana Dell’Osso
Dipartimento di Medicina Clinica e Sperimentale, Section of Psychiatry
University of Pisa
Pisa
Italy


Manuela P. Kaster
Department of Biochemistry, Center of Biological Sciences
Universidade Federal de Santa Catarina, Campus Universitário
Florianópolis, SC
Brazil


Mario Amore
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry
University of Genoa
Italy


Mary Kay Lobo
Department of Anatomy and Neurobiology
Mary Kay Lobo, Assistant Professor, University of Maryland School of Medicine
Baltimore, MD
USA


Michael Maes
Deakin University, Department of Psychiatry
Geelon
Australia


Morgana Moretti
Nutrition Post-Graduate Program, Universidade Federal de Santa Catarina, Campus Universitário
Florianópolis, SC
Brazil


Paolo Girardi
Department of Neuroscience, Mental Health and Sensory Organs – Sant’Andrea Hospital
Sapienza University of Rome
Italy


Renato T. Ramos
Laboratory of Psychophysiology and Virtual Reality (LIM-23) Department of Psychiatry
Faculty of Medicine, University of São Paulo
Brazil


Roger S. McIntyre
University of Toronto, University Health Network, Mood Disorders Psychopharmacology Unit
Toronto, Ontario
Canada


Stefano Baroni
Dipartimento di Medicina Clinica e Sperimentale, Section of Psychiatry
University of Pisa
Pisa
Italy


Stephanie E. Fulton
University of Montreal Hospital Research Center (CRCHUM); Departments of Nutrition; Neuroscience, University of Montreal; Montreal Diabetes Research Centre
Montreal, QC
Canada


Yena Lee
University of Toronto, University Health Network, Mood Disorders Psychopharmacology Unit
Toronto, Ontario
Canada


Young Sup Woo
Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Republic of
University of Toronto, University Health Network, Mood Disorders Psychopharmacology Unit
Toronto, Ontario
Canada




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