NYX-2925 is a novel N-methyl-D-aspartate receptor modulator that induces rapid and long-lasting analgesia in rat models of neuropathic pain

Nayereh Ghoreishi-Haack*, Jessica M. Priebe, Jacqueline D. Aguado, Elizabeth M. Colechio, Jeffrey S Burgdorf, M. Scott Bowers, Cassia N. Cearley, M. Amin Khan, Joseph R Moskal

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

NYX-2925 [(2S,3R)-3-hydroxy-2-((R)-5-isobutyryl-1-oxo-2,5-diazaspiro[3.4]octan-2-yl)butanamide] is a novel N-methyl-D-aspartate (NMDA) receptor modulator that is currently being investigated in phase 2 clinical studies for the treatment of painful diabetic peripheral neuropathy and fibromyalgia. Previous studies demonstrated that NYX-2925 is a member of a novel class of NMDA receptor-specific modulators that affect synaptic plasticity processes associated with learning and memory. Studies here examined NYX-2925 administration in rat peripheral chronic constriction nerve injury (CCI) and streptozotocin-induced diabetic mechanical hypersensitivity. Additionally, NYX-2925 was examined in formalin-induced persistent pain model and the tail flick test of acute nociception. Oral administration of NYX-2925 resulted in rapid and long-lasting analgesia in both of the neuropathic pain models and formalin-induced persistent pain, but was ineffective in the tail flick model. The analgesic effects of NYX-2925 were blocked by the systemic administration of NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid. Microinjection of NYX-2925 into the medial prefrontal cortex of CCI rats resulted in analgesic effects similar to those observed following systemic administration, whereas intrathecal administration of NYX-2925 was ineffective. In CCI animals, NYX-2925 administration reversed deficits seen in a rat model of rough-and-tumble play. Thus, it appears that NYX-2925 may have therapeutic potential for the treatment of neuropathic pain, and the data presented here support the idea that NYX-2925 may act centrally to ameliorate pain and modulate negative affective states associated with chronic neuropathic pain.

Original languageEnglish (US)
Pages (from-to)485-497
Number of pages13
JournalJournal of Pharmacology and Experimental Therapeutics
Volume366
Issue number3
DOIs
StatePublished - Sep 2018

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'NYX-2925 is a novel N-methyl-D-aspartate receptor modulator that induces rapid and long-lasting analgesia in rat models of neuropathic pain'. Together they form a unique fingerprint.

Cite this