[Latrepirdine: a systematic review of the preclinical studies]

Rev Neurol. 2015 Jan 1;60(1):35-42.
[Article in Spanish]

Abstract

We conduct a systematic review of the preclinical studies published to date involving the use of latrepirdine (Dimebon ®). Latrepirdine is capable of modulating different targets, such as those related with mitochondria, acetylcholinesterase activity or intraneuronal calcium levels, perhaps thanks to its action upon the N-methyl-D-aspartate-type receptor, which belongs to the glutamate family. The findings published on the possible effect of latrepirdine in protein aggregation processes in disorders such as Alzheimer's disease and Parkinson's disease are quite controversial. Likewise, the possible neuroprotective effect of latrepirdine has been evaluated in animal models of neurodegenerative diseases, again with heterogeneous results. Consequently, it can be concluded that no preclinical scientific evidence has been found to justify carrying out clinical trials.

Title: Latrepirdina: revision sistematica de los estudios preclinicos.

Se realiza una revision sistematica sobre los estudios preclinicos publicados en los que se utiliza latrepirdina (Dimebon ®). La latrepirdina es capaz de modular diferentes dianas, como las relacionadas con la mitocondria, la actividad de la acetilcolinesterasa o los niveles de calcio intraneuronales, quizas gracias a su accion sobre el receptor tipo N-metil-D-aspartato, de la familia del glutamato. Los resultados publicados sobre el posible efecto de la latrepirdina en procesos de agregacion proteica en trastornos como la enfermedad de Alzheimer y la enfermedad de Parkinson muestran una gran controversia. Asimismo, el posible efecto neuroprotector de la latrepirdina se ha evaluado en modelos animales de enfermedades neurodegenerativas, y muestra de nuevo resultados heterogeneos. Por todo ello, se concluye que no se ha localizado la evidencia cientifica preclinica que avale la realizacion de los ensayos clinicos.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Biological Availability
  • Calcium Signaling / drug effects
  • Cholinesterase Inhibitors / pharmacokinetics
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterase Inhibitors / therapeutic use
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Excitatory Amino Acid Antagonists / therapeutic use
  • Humans
  • Indoles / pharmacokinetics
  • Indoles / pharmacology
  • Indoles / therapeutic use*
  • Mice
  • Mitochondria / drug effects
  • Molecular Structure
  • Motor Neurons / drug effects
  • Neurodegenerative Diseases / chemically induced
  • Neurodegenerative Diseases / drug therapy*
  • Neurons / drug effects
  • Neuroprotective Agents / therapeutic use*
  • Parkinsonian Disorders / drug therapy
  • Protein Aggregation, Pathological / drug therapy
  • Rabbits
  • Rats
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Tissue Distribution

Substances

  • Cholinesterase Inhibitors
  • Excitatory Amino Acid Antagonists
  • Indoles
  • Neuroprotective Agents
  • Receptors, N-Methyl-D-Aspartate
  • latrepirdine