Therapeutic time windows of compounds against NMDA receptors signaling pathways for ischemic stroke

J Neurosci Res. 2021 Dec;99(12):3204-3221. doi: 10.1002/jnr.24937. Epub 2021 Oct 21.

Abstract

Much evidence has proved that excitotoxicity induced by excessive release of glutamate contributes largely to damage caused by ischemia. In view of the key role played by NMDA receptors in mediating excitotoxicity, compounds against NMDA receptors signaling pathways have become the most promising type of anti-stroke candidate compounds. However, the limited therapeutic time window for neuroprotection is a key factor preventing NMDA receptor-related compounds from showing efficacy in all clinical trials for ischemic stroke. In this perspective, the determination of therapeutic time windows of these kinds of compounds is useful in ensuring a therapeutic effect and accelerating clinical application. This mini-review discussed the therapeutic time windows of compounds against NMDA receptors signaling pathways, described related influence factors and the status of clinical studies. The purpose of this review is to look for compounds with wide therapeutic time windows and better clinical application prospect.

Keywords: NMDA receptor; cerebral ischemia; therapeutic time window.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain Ischemia* / drug therapy
  • Humans
  • Ischemic Stroke*
  • Neuroprotection
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Signal Transduction
  • Stroke* / drug therapy
  • Stroke* / metabolism

Substances

  • Receptors, N-Methyl-D-Aspartate