NRX-1074

NRX-1074
Systematic (IUPAC) name
(2S,3R)-2-{[(2S)-1-[(2R)-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]-2-benzylpyrrolidin-2-yl]formamido}-3-hydroxybutanamide
Legal status
Legal status
  • Investigational New Drug
Identifiers
UNII TTT1F11FZB YesY
Synonyms threonyl-prolyl-2R-(2-benzyl)-prolyl-threonine amide
Chemical data
Formula C25H37N5O6
Molar mass 503.60 g·mol−1

NRX-1074 (also known as AGN-241660) is a novel antidepressant, acting as a selective partial agonist of an allosteric site of the glycine site of the NMDA receptor complex, which is under investigation by Naurex (recently acquired by Allergan) for the treatment of major depressive disorder.[1][2][3][4] Its mechanism of action and effects are similar to those of rapastinel (GLYX-13), which is under development as an adjunctive therapy for treatment-resistant depression also by Naurex; however, NRX-1074 is 100-fold more potent by weight and, unlike GLYX-13 (which must be administered via intravenous injection), is orally-active.[3] NRX-1074 is intended by Naurex as an improved, follow-up drug to GLYX-13. The drug has shown rapid antidepressant effects in pre-clinical models of depression.[3] In addition, similarly to GLYX-13, it is well-tolerated and lacks the schizophrenia-like psychotomimetic effects of other NMDA receptor antagonists such as ketamine.[3] As of 2015, an intravenous formulation of NRX-1074 is in a phase II clinical trial for MDD,[3][5] and an oral formulation is concurrently in phase I trials for MDD.

See also

References

  1. ↑ Hayley S, Litteljohn D (2013). "Neuroplasticity and the next wave of antidepressant strategies". Front Cell Neurosci 7: 218. doi:10.3389/fncel.2013.00218. PMC: 3834236. PMID 24312008. Despite the mounting evidence indicating that ketamine has rapid and robust antidepressant properties (and notwithstanding the earlier mentioned preliminary clinical data indicating that long-term, low-dose ketamine may be both tolerable and effective; e.g., Messer et al., 2010), concerns over ketamine’s psychotomimetic effects have spurred intensive efforts to develop safer and more tolerable glutamate-based antidepressants. At the vanguard of this movement are the “next generation” NMDA receptor antagonists. Included here are the aminoadamantanes, memantine and amantadine (Sani et al., 2012); the NR2B-selective antagonists, traxoprodil (CP-101,606; Preskorn et al., 2008) and MK-0657 (Ibrahim et al., 2012a); and the low-affinity NMDA channel blocker AZD6765 (Zarate et al., 2013). The NMDA receptor glycine-site functional partial agonist, GLYX-13, and its orally bioavailable and presumed more potent analog, NRX-1074, have also garnered the recent attention of researchers and clinicians (Burgdorf et al., 2013; Dolgin, 2013), as have several modulators of metabotropic glutamate receptors (e.g., the mGluR7 allosteric agonist AMN082; Bradley et al., 2012) and select α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor potentiators (e.g., Org 26576; Nations et al., 2012).
  2. ↑ PR Newswire (2010). "Naurex's Novel Antidepressant GLYX-13 Recognized as One of Windhover's Top 10 Neuroscience Projects to Watch".
  3. 1 2 3 4 5 PR Newswire (2014). "Naurex Reports Positive Top-Line Phase 2b Results for Novel Antidepressant GLYX-13 and Advances NRX-1074 into Phase 2 Depression Study".
  4. ↑ Dang YH, Ma XC, Zhang JC, et al. (January 2014). "Targeting of NMDA Receptors in the Treatment of Major Depression". Curr. Pharm. Des. 20 (32): 5151–9. doi:10.2174/1381612819666140110120435. PMID 24410564.
  5. ↑ "Study of Intravenous NRX-1074 in Patients With Major Depressive Disorder". Clinicaltrials.gov. US National Institutes of Health. Retrieved 10 December 2014.

External links



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