Apimostinel

Investigational antidepressant compound
  • US: Investigational New Drug
Identifiers
  • (2R)-1-[(2S)-1-[(2S,3R)-2-Amino-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]-N-[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]-2-benzylpyrrolidine-2-carboxamide
CAS Number
  • 1421866-48-9
PubChem CID
  • 71249967
ChemSpider
  • 52085607
UNII
  • TTT1F11FZB
KEGG
  • D11299
ChEMBL
  • ChEMBL3545230
Chemical and physical dataFormulaC25H37N5O6Molar mass503.600 g·mol−13D model (JSmol)
  • Interactive image
  • C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N2CCC[C@@]2(Cc3ccccc3)C(=O)N[C@@H]([C@@H](C)O)C(N)=O
InChI
  • InChI=1S/C25H37N5O6/c1-15(31)19(26)23(35)29-12-6-10-18(29)22(34)30-13-7-11-25(30,14-17-8-4-3-5-9-17)24(36)28-20(16(2)32)21(27)33/h3-5,8-9,15-16,18-20,31-32H,6-7,10-14,26H2,1-2H3,(H2,27,33)(H,28,36)/t15-,16-,18+,19+,20+,25-/m1/s1
  • Key:DVBUEXCIEIAXPM-PJUQSVSOSA-N

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.[5][8]

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.[9] However, apimostinel is 1000-fold more potent in vitro and is intended as an improved, follow-up drug to rapastinel.[2][5] 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.[5] In addition, similarly to rapastinel, it is well tolerated and lacks the schizophrenia-like psychotomimetic effects of NMDA receptor antagonists such as ketamine.[5]

See also

References

  1. ^ "Naurex's Novel Antidepressant GLYX-13 Recognized as One of Windhover's Top 10 Neuroscience Projects to Watch". PR Newswire. 31 August 2010.
  2. ^ a b Henter ID, Park LT, Zarate CA (May 2021). "Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status". CNS Drugs. 35 (5): 527–543. doi:10.1007/s40263-021-00816-x. PMC 8201267. PMID 33904154.
  3. ^ Donello JE, Banerjee P, Li YX, Guo YX, Yoshitake T, Zhang XL, et al. (March 2019). "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. doi:10.1093/ijnp/pyy101. PMC 6403082. PMID 30544218.
  4. ^ Hayley S, Litteljohn D (November 2013). "Neuroplasticity and the next wave of antidepressant strategies". Frontiers in Cellular Neuroscience. 7: 218. doi:10.3389/fncel.2013.00218. PMC 3834236. PMID 24312008.
  5. ^ a b c d e "Naurex Reports Positive Top-Line Phase 2b Results for Novel Antidepressant GLYX-13 and Advances NRX-1074 into Phase 2 Depression Study". PR Newswire. 6 May 2014. Archived from the original on 14 July 2014.
  6. ^ "Allergan Successfully Completes Naurex Acquisition". Allergan plc (Press release). PR Newswire. Retrieved 2016-11-20.
  7. ^ "Home - Gate Neurosciences". Retrieved 2022-05-12.
  8. ^ Clinical trial number NCT02067793 for "Study of Intravenous NRX-1074 in Patients With Major Depressive Disorder" at ClinicalTrials.gov
  9. ^ Donello JE, Banerjee P, Li YX, Guo YX, Yoshitake T, Zhang XL, et al. (March 2019). "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. doi:10.1093/ijnp/pyy101. PMC 6403082. PMID 30544218.

External links

  • Apimostinel (NRX-1074) - AdisInsight
  • v
  • t
  • e
SSRIsTooltip Selective serotonin reuptake inhibitors
SNRIsTooltip Serotonin–norepinephrine reuptake inhibitors
NRIsTooltip Norepinephrine reuptake inhibitors
NDRIsTooltip Norepinephrine–dopamine reuptake inhibitors
NaSSAsTooltip Noradrenergic and specific serotonergic antidepressants
SARIsTooltip Serotonin antagonist and reuptake inhibitors
SMSTooltip Serotonin modulator and stimulators
Others
TCAsTooltip Tricyclic antidepressants
TeCAsTooltip Tetracyclic antidepressants
Others
Non-selective
MAOATooltip Monoamine oxidase A-selective
MAOBTooltip Monoamine oxidase B-selective
Miscellaneous
  • v
  • t
  • e
AMPARTooltip α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
KARTooltip Kainate receptor
NMDARTooltip N-Methyl-D-aspartate receptor
  • See also: Receptor/signaling modulators
  • Metabotropic glutamate receptor modulators
  • Glutamate metabolism/transport modulators