Nerinetide is a neuroprotective eicosapeptide designed to reduce ischemic brain injury by disrupting the interaction between N-methyl-D-aspartate (NMDA) receptors and downstream excitotoxic signaling.

It was tested in two major clinical trials for acute ischemic stroke:

• ESCAPE-NEXT Trial: Assessed Nerinetide in patients undergoing endovascular thrombectomy (EVT) without prior thrombolysis, finding no significant improvement in functional independence at 90 days.

• FRONTIER Trial: Evaluated prehospital Nerinetide administration within 3 hours of stroke onset, showing no overall benefit but potential efficacy in ischemic stroke patients receiving reperfusion therapy.

Although Nerinetide was safe, its clinical benefit remains uncertain, with timing and patient selection emerging as key factors for its potential role in stroke treatment. Further studies are needed to refine its use in combination with reperfusion therapies.