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Nerinetide is a synthetic eicosapeptide neuroprotectant developed for the treatment of acute ischemic stroke. It acts by disrupting the interaction between N-methyl-D-aspartate receptors (NMDARs) and post-synaptic density protein 95 (PSD-95), thereby attenuating excitotoxic neuronal cell death. Specifically, nerinetide uncouples PSD-95 from NMDARs and neuronal nitric oxide synthase (nNOS), reducing neurotoxic signaling cascades that lead to excessive nitric oxide production and neuronal injury during ischemia-reperfusion events. Unlike thrombolytics, it does not dissolve clots but aims to protect brain tissue from secondary damage following stroke onset[1][3][5][6]. Nerinetide has shown efficacy in preclinical models and has been evaluated in phase 2 and phase 3 clinical trials for acute ischemic stroke[3][4][6]. Its effectiveness appears reduced when administered with alteplase due to plasmin-mediated cleavage of the peptide[4][8].
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