Rapastinel

NMDA Receptor Modulator / Glutamatergic PeptideRx: ResearchCompound: Investigational

Also known as: GLYX-13, NRX-1074, Thr-Pro-Pro-Thr-NH2

Educational Only — Not medical advice. Consult a qualified clinician before using any peptide.

Summary

Rapastinel (formerly GLYX-13) is a tetrapeptide amide (Thr-Pro-Pro-Thr-NH2) that acts as a functional partial agonist at the NMDA receptor glycine site. It was investigated by Allergan/Naurex as a rapid-onset antidepressant for major depressive disorder (MDD), designed to avoid the dissociative side effects of ketamine. Phase III clinical trials failed to meet primary endpoints in 2019, and development was discontinued.

Mechanism of Action

Partial agonist at the glycine co-agonist site of the NMDA receptor (GluN1 subunit); modulates NMDA receptor activity without full blockade, enhancing synaptic plasticity and downstream AMPA receptor signaling, leading to rapid antidepressant effects.

Routes of Administration

IntravenousSubcutaneous

Goals & Uses

  • Treatment-resistant depressionPsychiatryLow
  • Rapid antidepressant effectPsychiatryLow
  • Synaptic plasticity enhancementNeuroscience / ResearchModerate
  • Major Depressive Disorder (MDD) treatmentPsychiatry / AntidepressantModerate

Contraindications

  • Known hypersensitivity to rapastinel or excipientsAllergyHigh

Adverse Effects

  • HeadacheNeurologicCommonPain in the head or upper neck
  • NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
  • Dissociative symptomsPsychiatric/NeurologicalRare
  • Infusion site reactionsLocalUncommon
  • DizzinessNeurologicCommonFeeling faint, lightheaded, or unsteady

Drug Interactions

  • Other NMDA receptor modulators (e.g., ketamine, memantine)Moderate
  • Antidepressants (SSRIs, SNRIs, MAOIs)Low

Population Constraints

  • Severe renal or hepatic impairmentOrgan FunctionRelative
  • PregnancyReproductive SafetyRelative
  • Pediatric patientsAgeRelative

Regulatory Status

  • European UnionUnapprovedNever received EMA approval; no marketing authorization application filed.
  • United StatesInvestigationalReceived FDA Breakthrough Therapy Designation for MDD (2014). Phase III trials failed (2019); development discontinued. Not approved.
  • United KingdomUnapprovedNot approved by MHRA. No licensed indication in the UK.

Received FDA Breakthrough Therapy Designation for MDD in 2014. Phase III trials (RECOVER, RADIANT, RESTORE) failed to demonstrate statistically significant efficacy over placebo. Development discontinued by Allergan in 2019. Not approved in any jurisdiction.

Evidence & Sources

No sources recorded yet.

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