Effects of Rapastinel (Formerly GLYX-13) on Serum Brain-Derived Neurotrophic Factor in Obsessive-Compulsive Disorder

Linkovski, Omer; Shen, Hanyang; Zwerling, Jordana; Filippou-Frye, Maria; Jo, Booil; Cordell, Elisabeth; Cooper, Thomas B.; Simpson, Helen Blair; Burch, Ronald M.; Moskal, Joseph R.; Lee, Francis; Rodriguez, Carolyn I.

doi:10.4088/jcp.17l11824

Cited by 4 publications

(2 citation statements)

References 18 publications

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“…A single administration of rapatinel has produced rapid antidepressant actions in clinical phase II [14] and preclinical rodent models [13,[16][17][18], without psychotomimetic or dissociative effects [19]. In addition to the antidepressant-like effects of rapastinel, improvements in anxiety, cognitive impairment, cerebral ischemia injury, post-traumatic stress disorder, autism, schizophrenia, and obsessive-compulsive disorder have been widely reported [20][21][22][23][24][25][26][27][28]. However, four recent phase III studies (ClinicalTrials.gov Identifiers NCT02932943, NCT02943564, NCT02943577, NCT02951988) on the use of rapastinel as an adjunctive compound for MDD did not identify rapid-acting antidepressant-like actions.…”

Section: Introductionmentioning

confidence: 99%

ERK/mTOR signaling may underlying the antidepressant actions of rapastinel in mice

Shen

Liu

et al. 2022

Transl Psychiatry

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Rapastinel as the allosteric modulator of N-methyl-D-aspartate receptor (NMDAR) produces rapid antidepressant-like effects dependent on brain-derived neurotrophic factor (BDNF) and VGF (nonacryonimic) release. Herein, we further explore the molecular mechanisms of the antidepressant effects of repeated administration with rapastinel in mice. Our results showed that continuous 3-day rapastinel (5 and 10 mg/kg, i.v.) produced antidepressant-like actions dependent on the increase in extracellular regulated protein kinase (ERK)/mammalian target of rapamycin (mTOR) signaling and downstream substrates p70S6 kinase (p70S6k) and the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), which may induce the expression of VGF and BDNF in the hippocampus and prefrontal cortex of mice. Furthermore, compared with a single treatment, our data indicated that 3-day repeated rapastinel treatment produced antidepressant-like actions accompanied by potentiation of ERK/mTOR/VGF/BDNF/tropomyosin-related kinase receptor B (TrkB) signaling. Based on previous and our supplementary data that showed the pivotal role of on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in the rapid release of VGF and BDNF and activation of TrkB by a single dose of rapastinel, we postulate that the antidepressant-like effects of single or repeated administration of rapastinel may result in the rapid release of VGF and BDNF or ERK/mTOR signaling pathway-mediated VGF/BDNF/TrkB autoregulatory feedback loop respectively. Our current work adds new knowledge to the molecular mechanisms that underlie the antidepressant-like actions of rapastinel in mice.

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Section: Introductionmentioning

confidence: 99%

ERK/mTOR signaling may underlying the antidepressant actions of rapastinel in mice

Shen

Liu

et al. 2022

Transl Psychiatry

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“…29 Interestingly, in a separate paper on the same OCD sample, the rapastinel's effect, contrary to what had been observed for ketamine, appeared to be correlated to a reduction of the Brain-Derived Neurotrophic Factor (BDNF). 30…”

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confidence: 99%

Investigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder

Grassi¹,

Cecchelli²,

Vignozzi³

et al. 2021

JEP

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Brain-derived neurotrophic factor as a biomarker for obsessive-compulsive disorder: A meta-analysis

Hao

Chen

et al. 2022

Journal of Psychiatric Research

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Effects of Rapastinel (Formerly GLYX-13) on Serum Brain-Derived Neurotrophic Factor in Obsessive-Compulsive Disorder

Abstract: To cite: Linkovski O, Shen H, Zwerling J, et al. Effects of rapastinel (formerly GLYX-13) on serum brain-derived neurotrophic factor in obsessivecompulsive disorder.

Cited by 4 publications

References 18 publications

ERK/mTOR signaling may underlying the antidepressant actions of rapastinel in mice

ERK/mTOR signaling may underlying the antidepressant actions of rapastinel in mice

Investigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder

Brain-derived neurotrophic factor as a biomarker for obsessive-compulsive disorder: A meta-analysis

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