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

Eur J Pharmacol. 2003 Feb 21;462(1-3):179-83. doi: 10.1016/s0014-2999(02)02945-x.


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.

MeSH terms

  • Animals
  • Cisplatin / administration & dosage
  • Foot / innervation
  • Male
  • Nerve Regeneration / drug effects*
  • Neural Conduction / drug effects
  • Neuroprotective Agents / pharmacology*
  • Peptides, Cyclic / pharmacology*
  • Peripheral Nervous System / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, Corticotropin / agonists*
  • Receptors, Melanocortin
  • Reflex / drug effects
  • Sciatic Nerve / injuries
  • Sciatic Nerve / physiology
  • Sciatic Neuropathy / etiology
  • Sciatic Neuropathy / physiopathology
  • Sciatic Neuropathy / prevention & control
  • alpha-MSH / analogs & derivatives*
  • alpha-MSH / pharmacology*


  • Neuroprotective Agents
  • Peptides, Cyclic
  • Receptors, Corticotropin
  • Receptors, Melanocortin
  • melanotan-II
  • alpha-MSH
  • Cisplatin