Neu2000, an NR2B-selective, moderate NMDA receptor antagonist and potent spin trapping molecule for stroke.

Abstract

Excess activation of ionotropic glutamate receptors, primarily N-methyl-D-aspartate (NMDA) receptors and free radicals, evoke nerve cell death following hypoxic-ischemic brain injury in various animal models. However, clinical trials in stroke patients using NMDA receptor antagonists have failed to show efficacy primarily due to the limited therapeutic time window for neuroprotection and a narrow therapeutic index. In comparison, antioxidants prolonged the time window for neuroprotection in animal models of ischemic stroke and showed greater therapeutic potential in clinical trials for ischemic stroke. Excess activation of NMDA receptors and free radicals mediate the two separate pathways of nerve cell death in stroke and a safe and multifunctional drug that can block both routes in the brain will likely provide a better therapeutic outcome in patients with stroke. Derivatives of the lead structures of sulfasalazine and aspirin have led to the discovery of a new molecule, Neu2000, that has demonstrated excellent neuroprotection against NMDA- and free radical-induced cell death. Neu2000 is an NR2B-selective, moderate NMDA receptor antagonist with potent cell-permeable, spin trapping antioxidant action even at nanomolar concentrations. Nonclinical and human phase I studies demonstrated that Neu2000 can be translated to treat patients with stroke with better efficacy and therapeutic time window.

• Authors: Sung Ig Cho, Ui Jin Park, Jun-Mo Chung, Byoung Joo Gwag
• Journal: Drug news & perspectives (Drug News Perspect) Vol. 23 Issue 9 Pg. 549-56 (Nov 2010) ISSN: 0214-0934 [Print] United States
• PMID: 21152450 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

Chemical References

• 2-hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino)benzoic acid
• Antioxidants
• Benzoates
• Fluorobenzenes
• Neuroprotective Agents
• Receptors, N-Methyl-D-Aspartate
• Salicylates
• meta-Aminobenzoates

Topics

• Animals
• Antioxidants (adverse effects, pharmacology)
• Benzoates (adverse effects, pharmacology)
• Brain Ischemia (drug therapy, physiopathology)
• Drug Delivery Systems
• Fluorobenzenes
• Humans
• Neuroprotective Agents (adverse effects, pharmacology)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Salicylates
• Spin Trapping
• Stroke (drug therapy, physiopathology)
• Time Factors
• meta-Aminobenzoates