In a recent study published in Nature , researchers developed the MK-801 bimodal drug that successfully cures obesity, hyperglycemia, and dyslipidemia in mouse models of metabolic illness by combining N-methyl-D-aspartate (NMDA) receptor antagonism with glucagon-like peptide-1 (GLP-1) receptor antagonism. Study: GLP-1-directed NMDA receptor antagonism for obesity treatment . Image Credit: Inside Creative House/Shutterstock.
com The NMDA receptor is a crucial brain cation channel influencing body weight homeostasis. Obesity is associated with glutamatergic neurotransmission and synaptic plasticity mediated by NMDA receptors . In mice, inhibiting NMDA receptor functions within the brainstem increases short-term dietary intake, but antagonizing them within the hypothalamus reduces food consumption and body weight.
NMDA receptor inhibitors, like MK-801 and memantine, lead to weight reduction in rats and reduced palatable food choices in rodents and non-human primates. These antagonists also inhibit binge eating in humans. In the present review, researchers developed a novel compound, MK-801, which combines a small-molecule antagonist with a peptide agonist to treat obesity.
MK-801 delivers a small-molecule modulator of an ionotropic receptor by targeting a G-protein-coupled receptor. To avoid the problems related to unspecific NMDA receptor blocking, the team created a peptide-based drug combination including MK-801, an NMDA receptor inhibitor, and a GLP-1 counterpart. They used r.
