The potent melanocortin receptor agonist melanotan-II promotes peripheral nerve regeneration and has neuroprotective properties in the rat.

The neurotrophic and neuroprotective potential of the alpha-melanocyte-stimulating hormone (alpha-MSH) analog cyclo-[Ac-Nle(4),Asp(5),D-Phe(7),Lys(10)]alpha-MSH-(4-10) amide (melanotan-II), a potent melanocortin receptor agonist, was investigated. The sciatic nerve crush model was used as a paradigm to investigate the neurotrophic properties of melanotan-II. Melanotan-II significantly enhanced the recovery of sensory function following a crush lesion of the sciatic nerve in the rat at a dose of 20 microg kg(-1) per 48 h, s.c., but not at a dose of 2 or 50 microg kg(-1). In addition, we observed that melanotan-II also possesses neuroprotective properties, as it partially protected the nerve from a toxic neuropathy induced by cisplatin. Thus, the present data for the first time demonstrate the effectiveness of the potent alpha-MSH analog melanotan-II in nerve regeneration and neuroprotection.