Newly Developed Drugs for Alzheimer's Disease in Relation to Energy Metabolism, Cholinergic and Monoaminergic Neurotransmission

Neuroscience. 2018 Feb 1:370:191-206. doi: 10.1016/j.neuroscience.2017.06.034. Epub 2017 Jul 1.

Abstract

Current options for Alzheimer's disease (AD) treatment are based on administration of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or memantine, acting as an N-methyl-D-aspartate (NMDA). Therapeutic approaches vary and include novel cholinesterase inhibitors, modulators of NMDA receptors, monoamine oxidase (MAO) inhibitors, immunotherapeutics, modulators of mitochondrial permeability transition pores (mPTP), amyloid-beta binding alcohol dehydrogenase (ABAD) modulators, antioxidant agents, etc. The novel trends of AD therapy are focused on multiple targeted ligands, where mostly ChE inhibition is combined with additional biological properties, positively affecting neuronal energy metabolism as well as mitochondrial functions, and possessing antioxidant properties. The present review summarizes newly developed drugs targeting cholinesterase and MAO, as well as drugs affecting mitochondrial functions.

Keywords: ABAD modulators; Alzheimer’s disease; cholinesterase inhibitors; mPTP modulators; monoamine oxidase (MAO) inhibitors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylcholine / metabolism*
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Animals
  • Biogenic Monoamines / metabolism*
  • Central Nervous System Agents / chemistry
  • Central Nervous System Agents / pharmacology*
  • Central Nervous System Agents / therapeutic use
  • Energy Metabolism / drug effects*
  • Humans
  • Synaptic Transmission / drug effects*
  • Synaptic Transmission / physiology

Substances

  • Biogenic Monoamines
  • Central Nervous System Agents
  • Acetylcholine