Nerinetide

Neuroprotective Peptide (PDZ Domain Inhibitor / Eicosanoid Pathway Modulator)Rx: InvestigationalCompound: Investigational

Also known as: NA-1, PSD-95 inhibitor peptide, Tat-NR2B9c

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

Summary

Nerinetide (NA-1) is an investigational neuroprotective peptide developed primarily for acute ischemic stroke. It targets the PSD-95/NMDA receptor/nNOS signaling complex to reduce excitotoxic neuronal death. In the ESCAPE-NA1 phase 3 trial, it did not meet its primary endpoint in the overall population but showed potential benefit in patients not receiving alteplase (tPA), suggesting a pharmacokinetic interaction with tPA may have attenuated its effect.

Mechanism of Action

Nerinetide is a cell-penetrating peptide that disrupts the interaction between PSD-95 (postsynaptic density protein 95) and neuronal nitric oxide synthase (nNOS) via inhibition of the PDZ2 domain of PSD-95. This uncoupling reduces excitotoxic nitric oxide production and downstream neuronal death following ischemia-reperfusion injury.

Routes of Administration

Intravenous

Goals & Uses

  • Prevention of delayed neuronal death post-ischemiaNeuroprotectionModerate
  • Reduction of infarct volume after endovascular thrombectomyNeurology / InterventionalModerate
  • Neuroprotection in acute ischemic strokeNeurology / StrokeModerate

Contraindications

  • Known hypersensitivity to nerinetide or any componentAllergyHigh

Adverse Effects

  • Overall adverse event profile similar to placeboGeneralCommon
  • HeadacheNeurologicUncommonPain in the head or upper neck
  • NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
  • Infusion-related reactionsHypersensitivityUncommon

Drug Interactions

  • Alteplase (tPA)High

Population Constraints

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

Regulatory Status

  • European UnionInvestigationalNot approved by EMA; evaluated under clinical trial authorization.
  • United StatesInvestigationalInvestigational new drug (IND) status; not FDA approved.
  • United KingdomInvestigationalNot approved by MHRA; investigational use only.

Not approved by FDA, EMA, or Health Canada. Evaluated in multiple clinical trials including the pivotal ESCAPE-NA1 phase 3 RCT (2020). Currently under further investigation in tPA-naive patient populations.

Evidence & Sources

No sources recorded yet.

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