GLYX-13 and Naurex NMDA Receptor Modulators

Moskal, J.R., Burch, R., Burgdorf, J.S., Kroes, R.A., Stanton, P.K., Disterhoft, J.F., Leander, J.D., 2014. GLYX-13, an NMDA receptor glycine site functional partial agonist enhances cognition and produces antidepressant effects without the psychotomimetic side effects of NMDA receptor antagonists. Expert Opin. Investig. Drugs 23, 243-54. Review article discussing the MOA of GLYX-13 that was investigated in preclinical studies as well as the pharmacology, pharmacokinetics and drug safety that were demonstrated in clinical studies

Burgdorf, J., Zhang, X.L., Nicholson, K.L., Balster, R.L., Leander, J.D., Stanton, P.K., Gross, A.L., Kroes, R.A., Moskal, J.R., 2013. GLYX-13, a NMDA receptor glycine-site functional partial agonist, induces antidepressant-like effects without ketamine-like side effects. Neuropsychopharmacology 38, 729-742. Demonstrates that GLYX-13 produces antidepressant-like effects in rat models without the side effects seen with ketamine, at least in part, by directly modulating NR2B-containing NMDARs in the medial pre-frontal cortex

Burgdorf, J., Zhang, X.L., Weiss, C., Matthews, E., Disterhoft, J.F., Stanton, P.K., and Moskal, J.R., 2011. The N-methyl-d-aspartate receptor modulator GLYX-13 enhances learning and memory, in young adult and learning impaired aging rats. Neurobiol Aging 32, 698-706. Demonstrates that GLYX-13 may be a promising treatment for deficits in cognitive function associated with aging

Burgdorf J, Kroes RA, Weiss C, Oh MM, Disterhoft JF, Brudzynski SM, Panksepp J, Moskal JR., 2011. Positive emotional learning is regulated in the medial prefrontal cortex by GluN2B-containing NMDA receptors. Neuroscience 192, 515-23. Shows that GLYX-13 facilitates positive emotional learning, which is relevant to the anhedonic symptoms of depression and schizophrenia

Moskal J.R., Burgdorf J, Kroes RA, Brudzynski SM, Panksepp J., 2011. A novel NMDA receptor glycine-site partial agonist, GLYX-13, has therapeutic potential for the treatment of autism. Neurosci Biobehav Rev. 35, 1982-88. Demonstrates that GLYX-13 may be a promising treatment for autism

Stanton, P.K., Potter, P.E., Aguilar, J., Decandia, M., Moskal, J.R., 2009. Neuroprotection by a novel NMDAR functional glycine site partial agonist, GLYX-13. Neuropharmacology and neurotoxicology 20, 1193-1197. Demonstrated that GLYX-13 reduced delayed death of CA1 pyramidal neurons in a model of brain trauma and that this neuroprotection was occluded using a glycine site full agonist, indicating that GLYX-13 acts by modulating activation of this site

Wood, P.L., Mahmood, S.A., and Moskal, J.R., 2008. Antinociceptive action of GLYX-13: an NMDA receptor glycine site partial agonist. Neuroreport 19, 1061-63. Demonstrates GLYX-13 efficacy in in vivo antinociceptive models compared to FDA approved neuropathic pain drug, gabapentin

Zhang, X.L., Sullivan, J.A., Moskal, J.R., and Stanton, P.K., 2008. A NMDA receptor glycine site partial agonist, GLYX-13, simultaneously enhances LTP and reduces LTD at Schaffer collateral-CA1 synapses in hippocampus. Neuropharmacology 55, 1238-1250. First evidence of GLYX-13 unique mechanism of action showing ability to increase LTP and decrease LTD

Moskal, J.R, Kuo, A.G, Weiss, C., Kelso, S., O’Connor Hanson, A., Wood, P.L., and Disterhoft, J.F., 2005. GLYX-13: monoclonal antibody-derived peptides that act as partial agonists at the glycine site of the N-methyl-D-aspartate receptor. Neuropharmacology 49, 1077-1087. First publication of GLYX-13 general NMDA properties relative to known NMDA programs; also describes the conversion of a monoclonal antibody into a small peptide mimetic with cognitive enhancing properties

Moskal, J.R., Yamamoto, H., and Colley, P.A., 2001. The use of antibody engineering to create novel drugs that target N-methyl-D-aspartate receptors. Current Drug Targets 2, 331-345. Review of GLYX-13 & its creation from a monoclonal antibody with NMDAR glycine site-specific partial antagonist properties

Thompson, L.T., Moskal, J.R., and Disterhoft, J.F., 1992. Hippocampus-dependent learning facilitated by a monoclonal antibody or D-cycloserine. Nature 359, 638-641. First report showing monoclonal antibody enhancement of learning and memory in an animal model

Moskal, J.R. and Schaffner, A.E., 1986. Monoclonal antibodies to the dentate gyrus: Immunocytochemical characterization and flow cytometric analysis of hippocampal neurons bearing unique cell-surface antigen. J. Neurosci. 6, 2045-2053. Seminal publication of original monoclonal antibody work