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The mechanism appears to involve increased serotonin synthesis in substantia nigra (both compacta and reticulata), a regional pattern unlike any existing antidepressant drug, plus potential dopaminergic contributions given the nigrostriatal location
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The diagram in d was created using BioRender
By substituting specific key residues in this middle domain, the molecular architecture of retatrutide selectively modulates the binding thermodynamics to achieve simultaneous receptor engagement without steric rejection
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