Rapastinel (GLYX-13)

Human clinical Cognitive Enhancement 3 sources

Rapastinel, also known as GLYX-13, is a synthetic tetrapeptide that acts as a rapid-acting antidepressant and cognitive enhancer. It functions as a partial agonist at the glycine site of the NMDA receptor, promoting neuroplasticity without the dissociative side effects typically associated with full NMDA antagonists like ketamine. While it showed significant promise in early clinical trials for major depressive disorder, Phase 3 trials did not meet their primary endpoints, though research continues into its neuroprotective and cognitive benefits.

01Dosing reference

Amount

5-10 mg/kg (IV in clinical trials) or 1-2 mg (SubQ in independent research)

Frequency

Once weekly or bi-weekly

Cycle

4-6 weeks on, followed by evaluation

Reference figures, not a recommendationThese values reflect amounts described in the literature and vendor documentation this database indexes. Use the reconstitution calculator to convert them into syringe units.

02Mechanism of action

NMDA Receptor Modulation

Rapastinel binds to the glycine site of the N-methyl-D-aspartate (NMDA) receptor as a partial agonist.

Glutamatergic Signaling Enhancement

This binding normalizes glutamatergic signaling and enhances long-term potentiation (LTP) in the hippocampus and medial prefrontal cortex.

Neuroplasticity and Synaptogenesis

The modulation leads to rapid synaptogenesis and increased dendritic spine density, which are associated with rapid antidepressant effects and cognitive enhancement.

03Human evidence

Rapid antidepressant effects within hours of administration.

Observed in Phase 2 clinical trials for treatment-resistant major depressive disorder, showing efficacy without psychotomimetic side effects.

Failed to separate from placebo in Phase 3 trials.

In large-scale Phase 3 trials for major depressive disorder, rapastinel did not meet the primary endpoint of significantly reducing depressive symptoms compared to placebo.

04Preclinical evidence

Enhanced learning and memory.

Demonstrated in various rodent models, showing improved performance in spatial memory and learning tasks.

Neuroprotective effects against stress.

Animal models of chronic stress showed that GLYX-13 prevented stress-induced synaptic deficits and behavioral despair.

05What is known vs. unknown

Reasonably established

Acts as a partial agonist at the NMDA receptor glycine site.
Produces rapid antidepressant-like effects in animal models and early human trials.
Does not cause the dissociative or psychotomimetic side effects associated with ketamine.
Enhances long-term potentiation (LTP) and neuroplasticity.

Unknowns & limits

The exact reasons for its failure in Phase 3 clinical trials for MDD remain a subject of investigation.
Long-term safety and efficacy in humans are not fully established.
Optimal dosing strategies for cognitive enhancement versus antidepressant effects are unclear.

06Safety & regulatory context

Regulatory statusRapastinel has generally been well-tolerated in clinical trials, with a side effect profile comparable to placebo and notably lacking the dissociative, psychotomimetic, or cardiovascular side effects seen with ketamine. It is not FDA-approved for any indication, having failed its Phase 3 clinical trials for major depressive disorder. It remains an investigational compound primarily used in research settings.

07Compared with Ketamine

Rapastinel (GLYX-13) vs. Ketamine

Key difference

While both modulate the NMDA receptor to produce rapid antidepressant effects, ketamine is a channel blocker (antagonist) that causes dissociative side effects, whereas rapastinel is a partial agonist at the glycine site with no dissociative effects.

When researchers discuss each

Ketamine is discussed as an established, albeit side-effect-heavy, rapid antidepressant, while rapastinel is discussed as a safer, non-dissociative alternative that modulates the same pathway but failed to show consistent efficacy in late-stage trials.

08Glossary

NMDA Receptor

A type of glutamate receptor in the brain that is critical for synaptic plasticity, memory, and learning.

Partial Agonist

A substance that binds to a receptor and activates it, but only with partial efficacy compared to a full agonist.

Long-Term Potentiation (LTP)

A persistent strengthening of synapses based on recent patterns of activity, widely considered one of the major cellular mechanisms that underlies learning and memory.

Psychotomimetic

Substances or effects that mimic the symptoms of psychosis, such as delusions or delirium, often seen with certain NMDA antagonists.

09Knowledge check

Q1What is the primary mechanism of action for Rapastinel (GLYX-13)?

Q2How does Rapastinel's side effect profile compare to ketamine in clinical studies?

Q3Which interpretation best matches the dossier's evidence regarding rapastinel's clinical trial results?

Q4When researchers contrast rapastinel and ketamine, which summary reflects the dossier's stated comparison context?

Q5Which statement accurately reflects rapastinel's safety and regulatory status according to the dossier?

10Sources

PubMed Rapastinel (GLYX-13), a rapid acting antidepressant
PubMed GLYX-13, an NMDA receptor glycine-site functional partial agonist
ClinicalTrials.gov Efficacy and Safety of Rapastinel in Major Depressive Disorder

More in Cognitive Enhancement

See all

Semax

Cognitive Enhancement

Human clinical

Semax is a synthetic peptide derived from adrenocorticotropic hormone (ACTH) that has been extensively studied for its neuroprotective and cognitive-enhancing properties. Research indicates it may modulate brain-derived neurotrophic factor (BDNF) and protect neurons from hypoxic damage, making it a subject of interest in stroke recovery and cognitive decline.

200-1000 mcg per day

Selank

Cognitive Enhancement

Human clinical

Selank is a synthetic heptapeptide analogue of the naturally occurring immunomodulatory peptide tuftsin. It has been extensively researched for its anxiolytic (anti-anxiety) and nootropic (cognitive-enhancing) properties, showing the ability to reduce stress and improve memory without the sedative side effects typical of traditional anti-anxiety medications.

250-500 mcg per day (often administered via nasal spray or SubQ)

Dihexa

Cognitive Enhancement

Preclinical only

Dihexa is an oligopeptide variant derived from angiotensin IV that binds to hepatocyte growth factor (HGF) and its receptor c-Met. Research in animal models suggests it has profound synaptogenic and neurogenic properties, showing potential for improving cognitive function and repairing brain damage in conditions like Alzheimer's disease and traumatic brain injury.

10-20 mg/day (oral/sublingual) or 2-5 mg/day (SubQ)

Research and educational use onlyNothing on this site is medical advice, a prescription, or a recommendation for human use. Compounds documented here are research chemicals. Consult a qualified clinician before making any health decision.