Discovery and Development of Non-Dopaminergic Agents for the Treatment of Schizophrenia: Overview of the Preclinical and Early Clinical Studies
| Autor: | Anna Partyka, Andrzej J. Bojarski, Grażyna Chłoń-Rzepa, Grzegorz Satała, Anna Wesołowska, Maciej Pawłowski, Agnieszka Jankowska |
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| Rok vydání: | 2019 |
| Předmět: |
Disease
Serotonergic Bioinformatics Biochemistry 03 medical and health sciences 0302 clinical medicine Glutamate homeostasis Drug Discovery medicine Animals Humans Dopamine hypothesis of schizophrenia 5-HT receptor 030304 developmental biology Pharmacology 0303 health sciences Molecular Structure business.industry Organic Chemistry medicine.disease Nicotinic acetylcholine receptor Schizophrenia Metabotropic glutamate receptor Molecular Medicine business 030217 neurology & neurosurgery Antipsychotic Agents |
| Zdroj: | Current Medicinal Chemistry. 26:4885-4913 |
| ISSN: | 0929-8673 |
| DOI: | 10.2174/0929867326666190710172002 |
| Popis: | Schizophrenia is a chronic psychiatric disorder that affects about 1 in 100 people around the world and results in persistent emotional and cognitive impairments. Untreated schizophrenia leads to deterioration in quality of life and premature death. Although the clinical efficacy of dopamine D2 receptor antagonists against positive symptoms of schizophrenia supports the dopamine hypothesis of the disease, the resistance of negative and cognitive symptoms to these drugs implicates other systems in its pathophysiology. Many studies suggest that abnormalities in glutamate homeostasis may contribute to all three groups of schizophrenia symptoms. Scientific considerations also include disorders of gamma-aminobutyric acid-ergic and serotonergic neurotransmissions as well as the role of the immune system. The purpose of this review is to update the most recent reports on the discovery and development of non-dopaminergic agents that may reduce positive, negative, and cognitive symptoms of schizophrenia, and may be alternative to currently used antipsychotics. This review collects the chemical structures of representative compounds targeting metabotropic glutamate receptor, gamma-aminobutyric acid type A receptor, alpha 7 nicotinic acetylcholine receptor, glycine transporter type 1 and glycogen synthase kinase 3 as well as results of in vitro and in vivo studies indicating their efficacy in schizophrenia. Results of clinical trials assessing the safety and efficacy of the tested compounds have also been presented. Finally, attention has been paid to multifunctional ligands with serotonin receptor affinity or phosphodiesterase inhibitory activity as novel strategies in the search for dedicated medicines for patients with schizophrenia. |
| Databáze: | OpenAIRE |
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