Apimostinel Explained

Apimostinel (GATE-202, formerly NRX-1074) is an investigational antidepressant, acting as a novel and selective modulator of the NMDA receptor.[1] [2] [3] [4] It is currently under development for the acute treatment of major depressive disorder (MDD) by Gate Neurosciences, and previously by Naurex and Allergan.[5] [6] [7] As of February 2015, an intravenous formulation of apimostinel has completed a phase IIa clinical trial for MDD.

Similar to rapastinel (GLYX-13), its mechanism of action acts through a unique binding site on the NMDA receptor, independent of the glycine site, to modulate receptor activity and enhance NMDAR-mediated synaptic plasticity.[8] However, apimostinel is 1000-fold more potent in vitro and is intended as an improved, follow-up drug to rapastinel. Similar to rapastinel, apimostinel is an amidated tetrapeptide, but has been structurally modified, via the addition of a benzyl group, to enhance its metabolic stability and pharmacokinetic profile. The drug has shown rapid and potent antidepressant effects in pre-clinical models of depression. In addition, similarly to rapastinel, it is well tolerated and lacks the schizophrenia-like psychotomimetic effects of NMDA receptor antagonists such as ketamine.

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Notes and References

  1. Web site: Naurex's Novel Antidepressant GLYX-13 Recognized as One of Windhover's Top 10 Neuroscience Projects to Watch . PR Newswire . 31 August 2010 .
  2. Henter ID, Park LT, Zarate CA . Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status . CNS Drugs . 35 . 5 . 527–543 . May 2021 . 33904154 . 8201267 . 10.1007/s40263-021-00816-x .
  3. Donello JE, Banerjee P, Li YX, Guo YX, Yoshitake T, Zhang XL, Miry O, Kehr J, Stanton PK, Gross AL, Burgdorf JS, Kroes RA, Moskal JR . 6 . Positive N-Methyl-D-Aspartate Receptor Modulation by Rapastinel Promotes Rapid and Sustained Antidepressant-Like Effects . The International Journal of Neuropsychopharmacology . 22 . 3 . 247–259 . March 2019 . 30544218 . 6403082 . 10.1093/ijnp/pyy101 .
  4. Hayley S, Litteljohn D . Neuroplasticity and the next wave of antidepressant strategies . Frontiers in Cellular Neuroscience . 7 . 218 . November 2013 . 24312008 . 3834236 . 10.3389/fncel.2013.00218 . free .
  5. Web site: Naurex Reports Positive Top-Line Phase 2b Results for Novel Antidepressant GLYX-13 and Advances NRX-1074 into Phase 2 Depression Study . https://web.archive.org/web/20140714112115/http://www.prnewswire.com/news-releases/naurex-reports-positive-top-line-phase-2b-results-for-novel-antidepressant-glyx-13-and-advances-nrx-1074-into-phase-2-depression-study-258089291.html . 14 July 2014 . PR Newswire . 6 May 2014 .
  6. Allergan Successfully Completes Naurex Acquisition . Allergan plc . PR Newswire . 2016-11-20.
  7. Web site: Home - Gate Neurosciences . 2022-05-12 . en-US.
  8. Donello JE, Banerjee P, Li YX, Guo YX, Yoshitake T, Zhang XL, Miry O, Kehr J, Stanton PK, Gross AL, Burgdorf JS, Kroes RA, Moskal JR . 6 . Positive N-Methyl-D-Aspartate Receptor Modulation by Rapastinel Promotes Rapid and Sustained Antidepressant-Like Effects . The International Journal of Neuropsychopharmacology . 22 . 3 . 247–259 . March 2019 . 30544218 . 6403082 . 10.1093/ijnp/pyy101 .

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