Mitochondrial Pharmacology of Dimebon (Latrepirdine) Calls for a New Look at its Possible Therapeutic Potential in Alzheimer's Disease

Autoren

Schamim H Eckert
Janett Gaca
Nathalie Kolesova
Kristina Friedland
Gunter P Eckert
Walter E Muller

DOI

10.14336/ad.2017.1014

ISSN

2152-5250

Ausgabe der Veröffentlichung

4

Zeitschrift

Aging and disease

Sprache

en

Paginierung

729 - 729

Datum der Veröffentlichung

2018

Status

Published

Herausgeber

Aging and Disease

Herausgeber URL

http://dx.doi.org/10.14336/ad.2017.1014

Datum der Datenerfassung

2021

Titel

Mitochondrial Pharmacology of Dimebon (Latrepirdine) Calls for a New Look at its Possible Therapeutic Potential in Alzheimer’s Disease

Ausgabe der Zeitschrift

9

Datenquelle: Crossref

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.

Addresses

1Department of Pharmacology, University of Frankfurt/M, Biocenter, D-60438 Frankfurt, Germany.

Autoren

Schamim H Eckert
Janett Gaca
Nathalie Kolesova
Kristina Friedland
Gunter P Eckert
Walter E Muller

DOI

10.14336/ad.2017.1014

eISSN

2152-5250

Externe Identifier

PubMed Identifier: 30090660
PubMed Central ID: PMC6065284

Open access

true

ISSN

2152-5250

Ausgabe der Veröffentlichung

4

Zeitschrift

Aging and disease

Sprache

eng

Medium

Electronic-eCollection

Online publication date

2018

Open access status

Open Access

Paginierung

729 - 744

Datum der Veröffentlichung

2018

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2018

Titel

Mitochondrial Pharmacology of Dimebon (Latrepirdine) Calls for a New Look at its Possible Therapeutic Potential in Alzheimer's Disease.

Sub types

review-article
Review
Journal Article

Ausgabe der Zeitschrift

9

Files

http://www.aginganddisease.org/EN/article/downloadArticleFile.do?attachType=PDF&id=147687 https://europepmc.org/articles/PMC6065284?pdf=render

Datenquelle: Europe PubMed Central

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.

Date of acceptance

2017

Autoren

Schamim H Eckert
Janett Gaca
Nathalie Kolesova
Kristina Friedland
Gunter P Eckert
Walter E Muller

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/30090660

DOI

10.14336/AD.2017.1014

Externe Identifier

PubMed Central ID: PMC6065284

ISSN

2152-5250

Ausgabe der Veröffentlichung

4

Zeitschrift

Aging Dis

Schlüsselwörter

Alzheimer disease
cognitive decline
dimebon
latrepirdine
mitochondrial dysfunction

Sprache

eng

Country

United States

Paginierung

729 - 744

PII

ad-9-4-729

Datum der Veröffentlichung

2018

Status

Published online

Titel

Mitochondrial Pharmacology of Dimebon (Latrepirdine) Calls for a New Look at its Possible Therapeutic Potential in Alzheimer's Disease.

Sub types

Journal Article
Review

Ausgabe der Zeitschrift

9

Datenquelle: PubMed

Mitochondrial Pharmacology of Dimebon (Latrepirdine) Calls for a New Look at its Possible Therapeutic Potential in Alzheimer's Disease

Files

Werkzeuge