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The constrained conformation additionally positions the pharmacophore residues (His, D-Phe, Arg, Trp) in an optimal spatial arrangement for simultaneous contact with the MC receptor binding pocket, which is why cyclic melanocortin analogs consistently demonstrate 10-100 fold greater potency than their linear counterparts in cAMP accumulation assays

These are illustrative concerns, not a contraindication checklist there is no approved indication

Irritation here causes more discomfort than elsewhere and can affect vision temporarily

Most patients regain significant weight within 1 year of stopping without behavioral support (STEP 1 extension data)