Screening of the Roche compound depository led to the identification of (1-benzyloxy-4,5-dihydro-1H-imidazol-2-yl)-butyl amine 4, a structurally novel NR1/2B subtype selective NMDA receptor antagonist. The structure-activity relationships developed in this series resulted in the discovery of a novel class of potent and selective NMDA receptor blockers displaying activity in vivo.
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Huntingtin plays an essential role in the adult hippocampus.
Neurobiol Dis
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Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada. Electronic address:
The consequences of non-pathogenic huntingtin (HTT) reduction in the mature brain are of substantial importance as clinical trials for numerous HTT-lowering therapies are underway; many of which are non-selective in that they reduce both mutant and wild type protein variants. In this study, we injected CaMKII-promoted AAV-Cre directly into the hippocampus of adult HTT floxed mice to explore the role of wild-type huntingtin (wtHTT) in adult hippocampal pyramidal neurons and the broader implications of its loss. Our findings reveal that wtHTT depletion results in profound macroscopic morphological abnormalities in hippocampal structure, accompanied by significant reactive gliosis.
View Article and Find Full Text PDFThe molecular mechanism of nitric oxide in memory consolidation and its role in the pathogenesis of memory-related disorders.
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Department of Surgery, Surgical Research Section, Hamad Medical Corporation, Doha, Qatar.
Memory is a dynamic process of encoding, storing, and retrieving information. It includes sensory, short-term, and long-term memory, each with unique characteristics. Nitric oxide (NO) is a biological messenger synthesized on demand by neuronal nitric oxide synthase (nNOS) through a biochemical process initiated by glutamate binding to NMDA receptors, causing membrane depolarization and calcium influx.
View Article and Find Full Text PDFInvestigating metabolic characteristics of type 2 diabetes mellitus-related cognitive dysfunction and correlating therapeutic effects of Di Dang Tang in animal models.
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January 2025
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China. Electronic address:
Ethnopharmacological Relevance: Di Dang Tang is a classic formula from Shang Han Lun, originally used to treat conditions such as blood stasis and heat accumulation. It is widely applied in the treatment of diabetes and its complications, but its effects on Type 2 Diabetes Mellitus-related Cognitive Dysfunction (T2DM-CD) remain unclear.
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Intranasal Administration of the Combination of Dextro-Ketamine and Dexmedetomidine for Treatment of Diabetic Neuropathic Pain in Rats.
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Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, Shandong, China.
-Methyl-d-aspartate (NMDA) receptors, a subtype of ionotropic glutamate receptors in the central nervous system (CNS), have garnered attention for their role in brain disorders. Specifically, GluN2A-containing NMDA receptors have emerged as a potential therapeutic target for the treatment of depressive disorders and epilepsy. However, the development of GluN2A-containing NMDA receptor-selective antagonists, represented by -(4-(2-benzoylhydrazine-1-carbonyl)benzyl)-3-chloro-4-fluorobenzenesulfonamide (TCN-201) and its derivatives, faces a significant challenge due to their limited ability to penetrate the blood-brain barrier (BBB), hampering their characterization and further advancement.
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