Autor: |
Ramakrishna Nirogi, Pradeep Jayarajan, Anil Shinde, Abdul Rasheed Mohammed, Venkata Ramalingayya Grandhi, Vijay Benade, Vinod Kumar Goyal, Renny Abraham, Venkat Jasti, Jeffrey Cummings |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
Biomolecules, Vol 13, Iss 2, p 309 (2023) |
Druh dokumentu: |
article |
ISSN: |
2218-273X |
DOI: |
10.3390/biom13020309 |
Popis: |
Serotonin (5-HT) plays an important role in the regulation of several basic functions of the central and peripheral nervous system. Among the 5-HT receptors, serotonin-6 (5-HT6) receptor has been an area of substantial research. 5-HT6 receptor is a G-protein-coupled receptor mediating its effects through diverse signaling pathways. Exceptional features of the receptors fueling drug discovery efforts include unique localization and specific distribution in the brain regions having a role in learning, memory, mood, and behavior, and the affinity of several clinically used psychotropic agents. Although non-clinical data suggest that both agonist and antagonist may have similar behavioral effects, most of the agents that entered clinical evaluation were antagonists. Schizophrenia was the initial target; more recently, cognitive deficits associated with Alzheimer’s disease (AD) or other neurological disorders has been the target for clinically evaluated 5-HT6 receptor antagonists. Several 5-HT6 receptor antagonists (idalopirdine, intepirdine and latrepirdine) showed efficacy in alleviating cognitive deficits associated with AD in the proof-of-concept clinical studies; however, the outcomes of the subsequent phase 3 studies were largely disappointing. The observations from both non-clinical and clinical studies suggest that 5-HT6 receptor antagonists may have a role in the management of neuropsychiatric symptoms in dementia. Masupirdine, a selective 5-HT6 receptor antagonist, reduced agitation/aggression-like behaviors in animal models, and a post hoc analysis of a phase 2 trial suggested potential beneficial effects on agitation/aggression and psychosis in AD. This agent will be assessed in additional trials, and the outcome of the trials will inform the use of 5-HT6 receptor antagonists in the treatment of agitation in dementia of the Alzheimer’s type. |
Databáze: |
Directory of Open Access Journals |
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