α‐Melanocyte‐stimulating hormone structure‐activity studies: Comparative analysis of melanotropic and CNS bioactivities

The structure‐activity relationships in vitro of α‐MSH (α‐melanocyte‐stimulating hormone, α‐melanotropin) analogs as determined on normal and transformed (melanoma cell) melanocyte bioassays are summarized. Specifically, the characterization of potent and metabolically stable melanotropic agonist analogs and a newly discovered antagonist of α‐MSH are highlighted. Comparison of these data versus the known structure‐activity relationships of α‐MSH related to CNS bioactivities suggests the existence of nonclassical α‐MSH receptor‐mediated pathways or, perhaps, a yet undefined endogenous neuropeptidergic pathway(s) having different selectivities for α‐MSH analogs. In summary, several of the α‐MSH analogs reported here may be useful molecular probes in future strategies aimed at the identification and systematic characterization of both peripheral and central α‐MSH receptors.