New strategies in the development of antidepressants: Towards the modulation of neuroplasticity pathways
| Autor: | Elena Castro, Verónica Inés Vargas, Elsa M. Valdizán, A. Rodríguez-Gaztelumendi, Fuencisla Pilar-Cuéllar, Ricardo Mostany, Álvaro Díaz, Raquel Linge, Begoña Treceño, Severiano dos Anjos, Angel Pazos, Rebeca Vidal |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Models Biological Serotonin 5-HT4 Receptor Agonists Internal medicine Neuroplasticity Monoaminergic Cannabinoid Receptor Modulators Drug Discovery medicine Animals Humans Pharmacology Neuronal Plasticity business.industry Depression Wnt signaling pathway Brain Long-term potentiation medicine.disease Endocannabinoid system Antidepressive Agents Monoamine neurotransmitter Endocrinology Mood disorders Antidepressant Receptors Serotonin 5-HT4 business Neuroscience Signal Transduction |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname ResearcherID |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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