On March 3, 2014, the U.S. FDA granted Fast Track designation to the development of rapastinel as an adjunctive therapy in treatment-resistant major depressive disorder. As of 2015, the drug had completed phase II clinical development for this indication. On January 29, 2016, Allergan (who acquired Naurex in July 2015) announced that rapastinel had received Breakthrough Therapy designation from the U.S. FDA for adjunctive treatment of major depressive disorder.
Rapastinel belongs to a group of compounds, referred to as glyxins (hence the original developmental code name of rapastinel, GLYX-13), that were derived via structural modification of B6B21, a monoclonal antibody that similarly binds to and modulates the NMDA receptor. The glyxins were invented by Joseph Moskal, the co-founder of Naurex. Glyxins and B6B21 do not bind to the glycine site of the NMDA receptor but rather to a different regulatory site on the NMDA receptor complex that serves to allosterically modulate the glycine site. As such, rapastinel is technically an allosteric modulator of the glycine site of the NMDA receptor, and hence is more accurately described as a functional glycine site weak partial agonist.
^Haring R, Stanton PK, Scheideler MA, Moskal JR (1991). "Glycine-like modulation of N-methyl-D-aspartate receptors by a monoclonal antibody that enhances long-term potentiation". J. Neurochem. 57 (1): 323–32. doi:10.1111/j.1471-4159.1991.tb02131.x. PMID1828831.
^Moskal JR, Kuo AG, Weiss C, Wood PL, O'Connor Hanson A, Kelso S, Harris RB, Disterhoft JF (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. PMID16051282.
^ abBurch RM, Amin Khan M, Houck D, Yu W, Burgdorf J, Moskal JR (2016). "NMDA Receptor Glycine Site Modulators as Therapeutics for Depression: Rapastinel has Antidepressant Activity without Causing Psychotomimetic Side Effects". Curr Neuropharmacol. PMID26830963.
^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. PMID16051282.
^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. PMID19623090.
^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. PMID18580579.