NPS 1506, a moderate affinity uncompetitive NMDA receptor antagonist: preclinical summary and clinical experience

  title={NPS 1506, a moderate affinity uncompetitive NMDA receptor antagonist: preclinical summary and clinical experience},
  author={Alan L. Mueller and Linda D. Artman and Manuel F. Balandrin and E Brady and Y Chien and Eric G. Delmar and A. Kierstead and Thomas B. Marriott and Scott T. Moe and Joanna L. Raszkiewicz and Bradford C. Vanwagenen and D. Wells},
  journal={Amino Acids},
Summary. NPS Pharmaceuticals, Inc. (NPS) has synthesized a series of open-channel blockers with varying potencies at the NMDA receptor. NPS 1506 (Fig. 1) is a moderate affinity antagonist that inhibits NMDA/glycine-induced increases in cytosolic calcium in cultured rat cerebellar granule cells (IC50 = 476 nM) and displaces the binding of [3H]MK-801 to rat cortical membranes (IC50 = 664 nM). 
Marked Prevention of Ischemic Brain Injury by Neu2000, an NMDA Antagonist and Antioxidant Derived from Aspirin and Sulfasalazine
  • B. Gwag, Young Ae Lee, S. Cho
  • Biology
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2007
2-Hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino)-benzoic acid (Neu2000) was derived from aspirin and sulfasalazine to prevent both NMDA neurotoxicity and oxidative stress and showed marked neuroprotection in a masked fashion in two rodent models of focal cerebral ischemia.
Clinical Trials with Drugs Targeting Ionic Channels, Antiporters, and Pumps in Ischemic Stroke
Despite the great concerted efforts to develop effective therapies for brain ischemia, the only successfully available therapy for acute stroke treatment is the recombinant tissue plasminogen
Acute treatment with MgSO4 attenuates long‐term hippocampal tissue loss after brain trauma in the rat
These findings are the first to demonstrate long‐term neuroprotection of hippocampal tissue by an acute treatment in a TBI model and show that the previously reported broad efficacy of MgSO4 or NPS 1506 observed shortly after brain trauma could not be detected 8 months post‐injury.
A Review of Neuroprotection Pharmacology and Therapies in Patients with Acute Traumatic Brain Injury
Examination of novel strategies addressing both pathological and pharmacological factors affecting outcome, employing novel trial design methods and utilizing biomarkers validated to be reflective of the prognosis for TBI will facilitate progress in overcoming the obstacles identified from previous clinical trials.
Reflections on Neuroprotection Research and the Path Toward Clinical Success
From retrospective analysis in rt-PA ineligible stroke patients, embolectomy alone has proven safe and beneficial if completed within 6 h.