Mitochondrial Pharmacology of Dimebon (Latrepirdine) Calls for a New Look at its Possible Therapeutic Potential in Alzheimer’s Disease 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
The Effects of Latrepirdine on Amyloid-β Aggregation and Toxicity Latrepirdine (Dimebon) has been demonstrated to be a neuroprotective and cognition improving agent in neurodegenerative diseases that feature protein aggregation and deposition, such as Alzheimer's disease (AD). The accumulation of amyloid-β (Aβ) protein aggregates is a key event in the neurodegenerative process in AD. This study explores if latrepirdine modulation of protein aggregation contributes to its neuroprotective mechanism of action. Assessment of neuronal cell death showed that there was a significant reduction in lactate dehydrogenase release at an equimolar ratio of Aβ:latrepirdine and with lower concentrations of latrepirdine. The ability of latrepirdine to alter the formation of Aβ42 aggregates was assessed
"Preconditioning" with latrepirdine, an adenosine 5'-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1G93A mice. Adenosine 5'-monophosphate-activated protein kinase (AMPK) is a master regulator of energy balance. As energy imbalance is documented as a key pathologic feature of amyotrophic lateral sclerosis (ALS), we investigated AMPK as a pharmacologic target in SOD1(G93A) mice. We noted a strong activation of AMPK in lumbar spinal cords of SOD1(G93A) mice. Pharmacologic activation of AMPK has shown protective effects in neuronal "preconditioning" models. We tested the hypothesis that "preconditioning" with a small molecule activator of AMPK, latrepirdine, exerts beneficial effects on disease progression. SOD1(G93A) mice (n
A Randomized, Double-blind, Placebo-Controlled Study of Latrepirdine in Patients With Mild to Moderate Huntington Disease. BACKGROUND Latrepirdine is an orally administered experimental small molecule that was initially developed as an antihistamine and subsequently was shown to stabilize mitochondrial membranes and function, which might be impaired in Huntington disease. OBJECTIVE To determine the effect of latrepirdine on cognition and global function in patients with mild to moderate Huntington disease. DESIGN Randomized, double-blind, placebo-controlled study. SETTING Sixty-four research centers in Australia, Europe, and North America. PATIENTS Four hundred three patients with mild to moderate Huntington disease and baseline cognitive impairment (Mini-Mental State Examination score, 10-26
to be implemented [3].Dementia So far, the lack of RCTs implies that no evidence-based therapeutic recommendations can be given. There is no evidence supporting the use of memantine. Cholinesterase inhibitors were ineffective [9, 10, 42–44]. Latrepirdin (Dimebon) showed no improvement in cognition or function [24].Speech therapy and occupational therapy with cognitive training might possibly be helpful [6].Sleep . International Journal of Language & Communication Disorders. 2021;56(2):330–345. doi: 10.1111/1460-6984.12604. [PubMed] [CrossRef] [Google Scholar]24. Group, H. I. o. t. H. S., & European Huntington's Disease, N A randomized, double-blind, placebo-controlled study of latrepirdine in patients with mild to moderate Huntington disease. Jama Neurology. 2013;70(1):25–33. doi: 10.1001/2013.jamaneurol.382. [PubMed
The rise and fall of Dimebon. Dimebon (latrepirdine) was developed and used in Russia as an over-the-counter oral antihistamine for allergy treatment. In the early 1990s, Dimebon was characterized as a low-affinity NMDA receptor antagonist by Dr. Sergey Bachurin and his colleagues. An initial small-scale, open-label trial of Dimebon in 14 Alzheimer's disease (AD) patients demonstrated potential
A randomized, placebo-controlled trial of latrepirdine in Huntington disease. To evaluate the safety and tolerability of latrepirdine in Huntington disease (HD) and explore its effects on cognition, behavior, and motor symptoms. Double-blind, randomized, placebo-controlled trial. Multicenter outpatient trial. Ninety-one participants with mild to moderate HD enrolled at 17 US and UK centers from July 18, 2007, through July 16, 2008. Latrepirdine, 20 mg 3 times daily (n = 46), or matching placebo (n = 45) for a 90-day treatment period. The primary outcome variable was tolerability, defined as the ability to complete the study at the assigned drug dosage. Secondary outcome variables included score changes from baseline to day 90 on the Unified Huntington's Disease Rating Scale (UHDRS
Dimebon disappointment. Dimebon (latrepirdine) has received widespread publicity as a potential therapy for Alzheimer's disease following a very positive phase 2 study carried out in Russia and published in the Lancet in 2008. In this study there were improvements over 6 months in all endpoints (cognitive, global, daily function and behaviour), with continuing improvement at 12 months