GLYX-13
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|---|---|
| GLYX-13 | |
| Systematic (IUPAC) name | |
| (S)-N-[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]-1-[(S)-1-((2S,3R)-2-amino-3-hydroxybutanoyl)pyrrolidine-2-carbonyl]pyrrolidine-2-carboxamide | |
| Clinical data | |
| Pregnancy cat. | ? (US) |
| Legal status | Investigational New Drug |
| Identifiers | |
| CAS number | 117928-94-6 |
| ATC code | None |
| Chemical data | |
| Formula | C18H31N5O6 |
| Mol. mass | 413.47 |
GLYX-13 is a partial agonist of the NMDA receptor - specifically at the glycine binding site. It has been shown to enhance memory and learning in both young adult and learning-impaired, aging rat models.[1] GLYX-13, a tetrapeptide, readily crosses the blood brain barrier and has been shown to increase Schaffer collateral-CA1 LTP in vitro. In concert with a learning task it has also been shown to elevate gene expression of hippocampal NR1, a subunit of the NMDA receptor, in 3-month-old rats.[2] Neuroprotective effects have also been demonstrated in Mongolian Gerbils by delaying the death of CA1, CA3, and dentate gyrus pyramidal neurons under glucose and oxygen-deprived conditions.[3] Preclinical data indicates that GLYX-13 has a therapeutic index of 500 or more, onset within 20 minutes of administration, and produces antidepressant-like effects lasting approximately two weeks following administration. Currently under development by Naurex Inc, the compound recently completed phase II trials as a treatment for those resistant or non-responsive to traditional antidepressants.[4]
Additionally, GLYX-13 has demonstrated antinociceptive activity, which is of particular interest, as both competitive and noncompetitive NMDA receptor antagonists are ataxic at analgesic doses, while GLYX-13 and other glycine subunit ligands are able to elicit analgesia at sub-ataxic doses.[5]
See also [edit]
References [edit]
- ^ Burgdorf, Jeffrey; Zhang, Xiao-lei; Weiss, Craig; Matthews, Elizabeth; Disterhoft, John F.; Stanton, Patric K.; Moskal, Joseph R. (2011). "The N-methyl-d-aspartate receptor modulator GLYX-13 enhances learning and memory, in young adult and learning impaired aging rats". Neurobiology of Aging 32 (4): 698–706. doi:10.1016/j.neurobiolaging.2009.04.012. PMC 3035742. PMID 19446371.
- ^ Moskal, Joseph R.; Kuo, Amy G.; Weiss, Craig; Wood, Paul L.; O'Connor Hanson, Amy; Kelso, Stephen; Harris, Robert B.; Disterhoft, John F. (2005). "GLYX-13: A monoclonal antibody-derived peptide that acts as an N-methyl-d-aspartate receptor modulator". Neuropharmacology 49 (7): 1077–87. doi:10.1016/j.neuropharm.2005.06.006. PMID 16051282.
- ^ Stanton, Patric K.; Potter, Pamela E.; Aguilar, Jennifer; Decandia, Maria; Moskal, Joseph R. (2009). "Neuroprotection by a novel NMDAR functional glycine site partial agonist, GLYX-13". NeuroReport 20 (13): 1193–7. doi:10.1097/WNR.0b013e32832f5130. PMID 19623090.
- ^ ClinicalTrials.gov NCT01234558 Single IV Dose of GLYX-13 in Patients With Treatment-Resistant Depression
- ^ Wood, Paul L.; Mahmood, Siddique A.; Moskal, Joseph R. (2008). "Antinociceptive action of GLYX-13: An N-methyl-D-aspartate receptor glycine site partial agonist". NeuroReport 19 (10): 1059–61. doi:10.1097/WNR.0b013e32830435c9. PMID 18580579.
