Dimebon (latrepirdine), an old antihistaminic drug, showed divergent results in two large clinical trials in Alzheimer disease (AD), which according to our review might be related to the specific pharmacological properties of the drug and the different patient populations included in both studies. Out of the many pharmacological effects of Dimebon, improvement of impaired mitochondrial function seeems to be most relevant for the substantial effects on cognition and behaviour reported in one of the studies, as these effects are already present at the low concentrations of dimebon measured in plasma and tissues of patients and experimental animals. Since impaired mitochondrial function seems to be the major driving force for the progression of the clinical symptoms and since most of the clinical benefits of dimebon originate from an effect on the symptomatic deterioration, mitochondrial improvement can also explain the lack of efficacy of this drug in another clinical trial where symptoms of the patiets remained stable for the time of the study. Accordingly, it seems worthwhile to reevaluate the clinical data to proof that clinical response is correlated with high levels of Neuropsychiatric Symptoms as these show a good relationship to the individual speed of symptomatic decline in AD patients related to mitochondrial dysfunction.
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http://dx.doi.org/10.14336/AD.2017.1014 | DOI Listing |
Curr Comput Aided Drug Des
January 2024
Department of Pharmaceutical Chemistry, C. L. Baid Metha College of Pharmacy, The Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu, India.
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June 2023
Molecular Science Laboratory, National Institute of Immunology, New Delhi 110067, India.
A series of novel γ-Carboline derivatives were designed and synthesized using the Suzuki coupling reaction to identify the leads for the activity against cancer. Interestingly, these compounds were tested for their anticancer activity against the cell lines, particularly human cancer cell lines MCF7 (breast), A549 (lung), SiHa (cervix), and Colo-205 (colon). Most of the γ-Carboline derivatives showed potent inhibitory activity in four cancer cell lines, according to in vitro anticancer activity screening.
View Article and Find Full Text PDFAdv Protein Chem Struct Biol
July 2023
Amity Institute of Neuropsychology and Neurosciences, Amity University Uttar Pradesh, Noida, India. Electronic address:
Aging is an inevitable phenomenon that causes a decline in bodily functions over time. One of the most important processes that play a role in aging is senescence. Senescence is characterized by accumulation of cells that are no longer functional but elude the apoptotic pathway.
View Article and Find Full Text PDFFront Pharmacol
February 2023
Biological Testing Laboratory, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Russia.
Pharmacokinetic characteristics as well as cognitive-enhancing nootropic activity of latrepirdine (Dimebon) in relationship with its polymorphic forms have been studied in SD and Wistar rats. The pharmacokinetics of six polymorphs (A, B, C, D, E, F) of latrepirdine were studied in male SD rats after 7 days of oral administration in corn oil at a dose of 10 mg/kg once a day. Blood and brain samples were taken on the 7th day of administration at 15 min, 30 min, 60 min and 120 min after administration and analyzed for latrepirdine content by LC-MS.
View Article and Find Full Text PDFBiomolecules
February 2023
Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, NV 89154, USA.
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-HT) receptor has been an area of substantial research. 5-HT receptor is a G-protein-coupled receptor mediating its effects through diverse signaling pathways.
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