Pharmacological and Electrophysiological Characterization of Novel NMDA Receptor Antagonists

ACS Chem Neurosci. 2018 Nov 21;9(11):2722-2730. doi: 10.1021/acschemneuro.8b00154. Epub 2018 Jun 1.

Abstract

This work reports the synthesis and pharmacological and electrophysiological evaluation of new N-methyl-d-aspartic acid receptor (NMDAR) channel blocking antagonists featuring polycyclic scaffolds. Changes in the chemical structure modulate the potency and voltage dependence of inhibition. Two of the new antagonists display properties comparable to those of memantine, a clinically approved NMDAR antagonist.

Keywords: Alzheimer’s disease; NMDA receptor; electrophysiology; glutamate; memantine; polycyclic amines.

Publication types

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

MeSH terms

  • Amines / chemical synthesis
  • Amines / pharmacology
  • Animals
  • Cerebellum / cytology
  • Excitatory Amino Acid Antagonists / chemical synthesis*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Inhibitory Concentration 50
  • Memantine / pharmacology
  • Neurons / drug effects*
  • Patch-Clamp Techniques
  • Polycyclic Compounds / chemical synthesis*
  • Polycyclic Compounds / pharmacology
  • Rats
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Amines
  • Excitatory Amino Acid Antagonists
  • Polycyclic Compounds
  • Receptors, N-Methyl-D-Aspartate
  • Memantine