The long-lasting antidepressant effects of rapastinel (GLYX-13) are associated with a metaplasticity process in the medial prefrontal cortex and hippocampus

Neuroscience
J BurgdorfJ R Moskal

Abstract

Rapastinel (GLYX-13) is an N-methyl-d-aspartate receptor (NMDAR) modulator that has characteristics of a glycine site partial agonist. Rapastinel is a robust cognitive enhancer and facilitates hippocampal long-term potentiation (LTP) of synaptic transmission in slices. In human clinical trials, rapastinel has been shown to produce marked antidepressant properties that last for at least one week following a single dose. The long-lasting antidepressant effect of a single dose of rapastinel (3mg/kg IV) was assessed in rats using the Porsolt, open field and ultrasonic vocalization assays. Cognitive enhancement was examined using the Morris water maze, positive emotional learning, and contextual fear extinction tests. LTP was assessed in hippocampal slices. Dendritic spine morphology was measured in the dentate gyrus and the medial prefrontal cortex. Significant antidepressant-like or cognitive enhancing effects were observed that lasted for at least one week in each model. Rapastinel facilitated LTP 1day-2weeks but not 4weeks post-dosing. Biweekly dosing with rapastinel sustained this effect for at least 8weeks. A single dose of rapastinel increased the proportion of whole-cell NMDAR current contributed by NR2B-containing NMDARs in...Continue Reading

References

Feb 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·P K Stanton
Apr 1, 1996·Trends in Neurosciences·W C Abraham, M F Bear
Feb 25, 2000·Biological Psychiatry·R M BermanJ H Krystal
Feb 26, 2003·European Journal of Pharmacology·Laetitia Prut, Catherine Belzung
Feb 26, 2003·European Journal of Pharmacology·Connie Sánchez
Aug 9, 2006·Archives of General Psychiatry·Carlos A ZarateHusseini K Manji
Dec 7, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Benjamin J HallAnirvan Ghosh
Apr 11, 2008·Nature Reviews. Neuroscience·Wickliffe C Abraham
Nov 11, 2008·Progress in Neuro-psychopharmacology & Biological Psychiatry·Anteneh M FeyissaBeata Karolewicz
May 28, 2009·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Rodrigo Machado-VieiraCarlos A Zarate
Oct 20, 2009·Trends in Pharmacological Sciences·Phil SkolnickRamon Trullas
Nov 10, 2009·Biological Psychiatry·Marije aan het RotSanjay J Mathew
Jan 19, 2010·Cerebral Cortex·Gal Richter-Levin, Mouna Maroun
Dec 15, 2010·Neuroscience and Biobehavioral Reviews·Jeffrey BurgdorfJoseph R Moskal
Oct 4, 2011·Current Opinion in Neurobiology·Miquel Bosch, Yasunori Hayashi
Sep 11, 2012·Progress in Neuro-psychopharmacology & Biological Psychiatry·Lin ZhangShu Yan Yu
Jan 11, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jeffrey BurgdorfJoseph R Moskal
Apr 23, 2013·Trends in Neurosciences·Sarah R HulmeWickliffe C Abraham
May 22, 2013·Molecular Psychiatry·K MartinowichH K Manji
Jun 4, 2013·Biological Psychiatry·John H KrystalRonald S Duman
Apr 15, 2014·Nature Medicine·Kristie T OtaRonald S Duman
Jan 13, 2015·Scientific Reports·Sho HasegawaAkihiko Ogura

❮ Previous
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Citations

Oct 26, 2016·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Rosaline V WaworuntuBrian M Berg
Oct 21, 2016·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Rong-Jian LiuRonald S Duman
May 16, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yeli GongZhe Xiong
Mar 14, 2018·Molecular Psychiatry·P Zanos, T D Gould
Mar 17, 2018·Nature Reviews. Neuroscience·Marc P ForrestPeter Penzes
Mar 9, 2018·CNS Drugs·Panos ZanosTodd D Gould
Feb 2, 2018·Acta Neuropsychiatrica·Vitor Silva Pereira, Vinícius Antonio Hiroaki-Sato
Dec 27, 2018·Expert Opinion on Investigational Drugs·Renee-Marie RagguettRoger S McIntyre
Oct 10, 2018·Annual Review of Pharmacology and Toxicology·Todd D GouldScott M Thompson
Dec 14, 2018·The International Journal of Neuropsychopharmacology·John E DonelloJoseph R Moskal
Nov 18, 2018·The International Journal of Neuropsychopharmacology·Bashkim KadriuCarlos A Zarate
Jul 11, 2018·The Journal of Pharmacology and Experimental Therapeutics·Nayereh Ghoreishi-HaackJoseph R Moskal
Feb 7, 2017·Neural Plasticity·Lulu Yao, Qiang Zhou
Feb 9, 2018·Journal of Drug and Alcohol Research·Olubukola KalejaiyeYousef Tizabi
Apr 27, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wenchao LiLiangren Zhang
May 12, 2017·Neural Plasticity·Yu-Jhen HuangChieh-Hsin Lin
Mar 22, 2019·Molecular Psychiatry·Ronald S DumanBrendan Hare
Nov 3, 2016·The Mental Health Clinician·Robert W Schmidt, Meghan L Thompson
Jul 10, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ya-Ting WangYi Zhang
Sep 19, 2019·Journal of Agricultural and Food Chemistry·Francesca CaracciGiulio Maria Pasinetti
Oct 1, 2021·CNS Spectrums·Xenia GondaFrank I Tarazi

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