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Supported by the substantial weight-loss efficacy of the GLP-1–MK-801 conjugate and the potentiated hypothalamic changes in transcripts and proteins related to NMDA receptor-linked neuroplasticity, the alteration in MK-801 biodistribution governed by GLP-1-mediated targeting may effectively bypass the delivery of MK-801 to vagal afferent target neurons in the nucleus of the solitary tract