Eckert 2017 Aging Dis
|Eckert SH, Gaca J, Kolesova N, Friedland K, Eckert GP, Muller WE (2017) Mitochondrial pharmacology of Dimebon (Latrepirdine) calls for a new look at its possible therapeutic potential in Alzheimer’s Disease. Aging Dis 10.14336/AD.2017.1014.|
Abstract: 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.
Labels: MiParea: Respiration, Pharmacology;toxicology Pathology: Alzheimer's
Organism: Human Tissue;cell: Kidney, HEK
Coupling state: OXPHOS, ET Pathway: N, CIV, NS HRR: Oxygraph-2k