Evaluation of nicotine and cotinine analogs as potential neuroprotective agents for Alzheimer's disease

Bioorg Med Chem Lett. 2014 Mar 15;24(6):1472-8. doi: 10.1016/j.bmcl.2014.02.008. Epub 2014 Feb 14.

Abstract

The currently available therapies for Alzheimer's disease (AD) and related forms of dementia are limited by modest efficacy, adverse side effects, and the fact that they do not prevent the relentless progression of the illness. The purpose of the studies described here was to investigate the neuroprotective effects of the nicotine metabolite cotinine as well as a small series of cotinine and nicotine analogs (including stereoisomers) and to compare their effects to the four clinically prescribed AD therapies.

Keywords: Amyloid; Dementia; Disease modifying; Excitotoxicity; Glutamate; Multi-target-directed ligands; Multifunctional compounds; Neurodegeneration; Neuroprotection; Nicotinic.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / drug therapy
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cotinine / chemistry*
  • Cotinine / pharmacology
  • Cotinine / therapeutic use
  • Humans
  • Neurons / cytology
  • Neurons / drug effects
  • Neuroprotective Agents / chemistry*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Nicotine / chemistry*
  • Nicotine / pharmacology
  • Nicotine / therapeutic use
  • Peptide Fragments / chemistry
  • Peptide Fragments / toxicity
  • Rats
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Peptide Fragments
  • Receptors, N-Methyl-D-Aspartate
  • amyloid beta-protein (1-42)
  • Nicotine
  • Cotinine