Rapastinel acetate  (Synonyms: GLYX-13 acetate)

Rapastinel (GLYX-13) acetate is a potent NMDAR modulator capable of crossing the blood-brain barrier, and it exhibits extremely high affinity for human NMDAR (EC₅₀=0.0017-9.9 nM). Rapastinel acetate enhances ERK signaling and activates the mTOR pathway, thereby upregulating the expression of BDNF and VGF, and inducing significant neuroplastic changes such as enhanced LTP and increased mature dendritic spine density in the hippocampus. Rapastinel acetate moderately elevates the efflux of dopamine, norepinephrine and 5-HT in the prefrontal cortex, and uniquely avoids side effects of traditional antidepressants such as dissociation, addiction or sedation. Rapastinel acetate is applicable to the research of major depressive disorder and hepatocellular carcinoma^{[1][2][3][4][5]}.

Rapastinel acetate (20 μM; 4 h) reverses the propofol-induced reductions in CaMKII phosphorylation, AKT phosphorylation, HIF-1α expression, intracellular Ca²⁺ concentration, glycolysis protein levels, adhesion molecule levels, and tumor cell-endothelial cell adhesion in Huh7 tumor conditioned medium-treated HUVECs^[2].
Rapastinel acetate (tested concentrations; 15 min preincubation, 15 min with [³H] MK-801) partially enhances [³H] MK-801 binding to recombinant human NR2A-, NR2B-, NR2C-, and NR2D-containing NMDARs with EC₅₀ values of 9.8 pM, 9.9 nM, 2.2 pM, and 1.7 pM, respectively^[5].
Rapastinel acetate (100 nM-1 μM) has its modulatory effects on NMDAR-mediated calcium mobilization completely abolished by mutations of critical amino acids in the NR2A^(R392E) or NR2B^(R393E) NMDAR amino terminal domain, confirming this domain is required for rapastinel's activity^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Rapastinel (5-10 mg/kg; intravenous injection, once daily for 3 consecutive days) acetate exerts rapid antidepressant-like effects in mice with CUS-induced depression, reverses behavioral deficits, and normalizes the ERK/mTOR/VGF/BDNF signaling pathway in the hippocampus and prefrontal cortex (PFC); in contrast, Rapastinel (0.5 mg/kg; intravenous injection, once daily for 3 consecutive days) acetate shows no activity^[1].
A single intravenous administration of Rapastinel (3 mg/kg) acetate produces sustained antidepressant-like and anxiolytic-like effects in male Sprague-Dawley rats for at least 1 week, as evidenced by significant changes in ultrasonic vocalizations, time spent in the central zone of the open field test, and immobility time in the Porsolt forced swim test. It also induces sustained cognitive-enhancing effects, as reflected by improved behavioral performance of rats in spontaneous alternation, positive affective learning, Morris water maze, and contextual fear extinction tests^[3].
Rapastinel (1 mg/kg; subcutaneous injection; twice daily; administered for 3 or 5 days) acetate reverses subchronic Phencyclidine-induced novel object recognition (NOR) impairment for at least 9 or 10 weeks, respectively, whereas Rapastinel (1 mg/kg; subcutaneous injection; 30 minutes in advance; single dose) acetate only transiently reverses NOR function when the test interval is 24 hours^[4].
Rapastinel (10-30 mg/kg; subcutaneous injection; single administration) acetate produces rapid and sustained antidepressant-like effects in rats, corresponding to concentrations of approximately 30 nM and ~100 nM in the medial prefrontal cortex (mPFC), respectively^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

473.52

C₂₀H₃₅N₅O₈

491872-39-0

CC(O)=O.O=C(N(CCC1)[C@@H]1C(N[C@H](C(N)=O)[C@H](O)C)=O)[C@H](CCC2)N2C([C@@H](N)[C@H](O)C)=O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Shen M, et al. ERK/mTOR signaling may underlying the antidepressant actions of rapastinel in mice. Transl Psychiatry. 2022;12(1):522. Published 2022 Dec 22.  [Content Brief]

  [2]. Qi J, et al. Propofol attenuates the adhesion of tumor and endothelial cells through inhibiting glycolysis in human umbilical vein endothelial cells. Acta Biochim Biophys Sin (Shanghai). 2019;51(11):1114-1122.  [Content Brief]

  [3]. Burgdorf J, et al. The long-lasting antidepressant effects of rapastinel (GLYX-13) are associated with a metaplasticity process in the medial prefrontal cortex and hippocampus. Neuroscience. 2015;308:202-211.  [Content Brief]

  [4]. Rajagopal L, et al. Repeated administration of rapastinel produces exceptionally prolonged rescue of memory deficits in phencyclidine-treated mice. Behav Brain Res. 2022;432:113964.  [Content Brief]

  [5]. Donello JE, et al. Positive N-Methyl-D-Aspartate Receptor Modulation by Rapastinel Promotes Rapid and Sustained Antidepressant-Like Effects. Int J Neuropsychopharmacol. 2019;22(3):247-259.  [Content Brief]