Abstract
Over the past five decades, the pharmacological treatment of depression has been based on the pathophysiological hypothesis of a deficiency in monoamines, mainly serotonin and noradrenaline. Antidepressants prescribed today, all of them designed to enhance central monoaminergic tone, present several important limitations, including a 2-5 weeks response lag and also a limited clinical efficacy. As it is increasingly evident that the abnormalities associated to depression go beyond monoamines, the development of better antidepressants will depend on the identification and understanding of new cellular targets. In this regard, much evidence supports a role for cellular and molecular mechanisms of neuroplasticity, including neurotrophic inputs, in mood disorders, in parallel with the biological features associated to stress conditions. In order to illustrate the possible relevance of neuroplasticity-related pathways for the therapy of depressive states, we here review the biological evidence supporting some therapeutic strategies in a very initial phase of development (modulation of the Wnt/GSK-3β/β-catenin pathway, potentiation of endocannabinoid activity, agonism of 5-HT4 receptors), which involve modulation of downstream mechanisms and neuroplasticity circuits. These strategies also show the existence of mixed mechanisms of action, constituting a nexus between the “classic” aminergic theory and the “new” neuroplasticity hypothesis.
Keywords: Antidepressant, stress, neuroplasticity, endocannabinoid, 5-HT4 receptors
Current Pharmaceutical Design
Title: New Strategies in the Development of Antidepressants: Towards the Modulation of Neuroplasticity Pathways
Volume: 17 Issue: 5
Author(s): Rebeca Vidal, Fuencisla Pilar-Cuellar, Severiano dos Anjos, Raquel Linge, Begona Treceno, Veronica Ines Vargas, Antonio Rodriguez-Gaztelumendi, Ricardo Mostany, Elena Castro, Alvaro Diaz, Elsa M. Valdizan and Angel Pazos
Affiliation:
Keywords: Antidepressant, stress, neuroplasticity, endocannabinoid, 5-HT4 receptors
Abstract: Over the past five decades, the pharmacological treatment of depression has been based on the pathophysiological hypothesis of a deficiency in monoamines, mainly serotonin and noradrenaline. Antidepressants prescribed today, all of them designed to enhance central monoaminergic tone, present several important limitations, including a 2-5 weeks response lag and also a limited clinical efficacy. As it is increasingly evident that the abnormalities associated to depression go beyond monoamines, the development of better antidepressants will depend on the identification and understanding of new cellular targets. In this regard, much evidence supports a role for cellular and molecular mechanisms of neuroplasticity, including neurotrophic inputs, in mood disorders, in parallel with the biological features associated to stress conditions. In order to illustrate the possible relevance of neuroplasticity-related pathways for the therapy of depressive states, we here review the biological evidence supporting some therapeutic strategies in a very initial phase of development (modulation of the Wnt/GSK-3β/β-catenin pathway, potentiation of endocannabinoid activity, agonism of 5-HT4 receptors), which involve modulation of downstream mechanisms and neuroplasticity circuits. These strategies also show the existence of mixed mechanisms of action, constituting a nexus between the “classic” aminergic theory and the “new” neuroplasticity hypothesis.
Export Options
About this article
Cite this article as:
Vidal Rebeca, Pilar-Cuellar Fuencisla, dos Anjos Severiano, Linge Raquel, Treceno Begona, Ines Vargas Veronica, Rodriguez-Gaztelumendi Antonio, Mostany Ricardo, Castro Elena, Diaz Alvaro, M. Valdizan Elsa and Pazos Angel, New Strategies in the Development of Antidepressants: Towards the Modulation of Neuroplasticity Pathways, Current Pharmaceutical Design 2011; 17 (5) . https://dx.doi.org/10.2174/138161211795164086
DOI https://dx.doi.org/10.2174/138161211795164086 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Stroke in Women
Recent Patents on Cardiovascular Drug Discovery Necessity for Re-Vascularization after Spinal Cord Injury and the Search for Potential Therapeutic Options
Current Neurovascular Research Use of BNP and CRP as Biomarkers in Assessing Cardiovascular Disease:Diagnosis Versus Risk
Current Vascular Pharmacology Effects of Brain IKKβ Gene Silencing by Small Interfering RNA on P-Glycoprotein Expression and Brain Damage in the Rat Kainic Acid-Induced Seizure Model
CNS & Neurological Disorders - Drug Targets Emerging Drugs and Indications for Cardio-Metabolic Disorders in People with Severe Mental Illness
Current Pharmaceutical Design Adult Stem Cells and Bioengineering Strategies for the Treatment of Cerebral Ischemic Stroke
Current Stem Cell Research & Therapy Role of Cation-Chloride-Cotransporters (CCC) in Pain and Hyperalgesia
Current Topics in Medicinal Chemistry Exercise Preconditioning Reduces Brain Damage and Inhibits TNF-α Receptor Expression after Hypoxia/Reoxygenation: An In Vivo and In Vitro Study
Current Neurovascular Research Induction of Myocardial Fibrosis and Hypertrophy by Natriuretic Peptides
Vascular Disease Prevention (Discontinued) Purinergic Signalling: What is Missing and Needed Next? The Use of Transgenic Mice, Crystallographic Analysis and MicroRNA
CNS & Neurological Disorders - Drug Targets Role of Methylene Blue in Trauma Neuroprotection and Neuropsychiatric Diseases
CNS & Neurological Disorders - Drug Targets Possibilities of Poly(D,L-lactide-co-glycolide) in the Formulation of Nanomedicines Against Cancer
Current Drug Targets PDE5 Inhibitor Treatment Options for Urologic and Non-Urologic Indications: 2012 Update
Current Pharmaceutical Design Targeting Mitochondrial Bioenergetics for Alzheimers Prevention and Treatment
Current Pharmaceutical Design Neuroimaging of Consciousness and Sleep Spindles
Recent Patents on Medical Imaging Misoprostol Reverse Hippocampal Neuron Cyclooxygenase-2 Downstream Signaling Imbalance in Aluminum-Overload Rats
Current Alzheimer Research Tamoxifen as a Powerful Neuroprotectant in Experimental Stroke and Implications for Human Stroke Therapy
Recent Patents on CNS Drug Discovery (Discontinued) Neural Stem Cells as Biological Minipumps: A Faster Route to Cell Therapy for the CNS?
Current Stem Cell Research & Therapy In Vitro and In Vivo Models of Multiple Sclerosis
CNS & Neurological Disorders - Drug Targets Brain Structural Effects of Antidepressant Treatment in Major Depression
Current Neuropharmacology