Design, synthesis, and evaluation of polyamine-memantine hybrids as NMDA channel blockers

Bioorg Med Chem. 2018 Feb 1;26(3):603-608. doi: 10.1016/j.bmc.2017.12.021. Epub 2017 Dec 16.

Abstract

N-Methyl-d-aspartate (NMDA) receptors have been implicated in learning and memory, and may also play a central role in various conditions leading to neuronal degradation. NMDA receptor antagonists could therefore be of therapeutic benefit for a number of neurological disorders. We have designed hybrid compounds of polyamines and memantine, both of which function as NMDA channel blockers. The triamine derivative with a guanidine moiety showed more potent antagonistic activity than memantine.

Keywords: Alzheimer’s disease; Guanidine; Memantine; NMDA channel blocker; Polyamine.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Drug Design*
  • Memantine / chemistry*
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / pharmacology
  • Oocytes / drug effects
  • Oocytes / physiology
  • Patch-Clamp Techniques
  • Polyamines / chemistry*
  • Protein Binding
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Xenopus laevis / growth & development

Substances

  • Neuroprotective Agents
  • Polyamines
  • Receptors, N-Methyl-D-Aspartate
  • Memantine