The potent melanocortin receptor agonist melanotan-II promotes peripheral nerve regeneration and has neuroprotective properties in the rat
Mariël P. Ter Laak, Jan H. Brakkee, Roger A. H. Adan, Frank P. T. Hamers and Willem Hendrik Gispen,
Department of Medical Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
Received 13 December 2002; accepted 19 December 2002. ; Available online 1 February 2003.
Abstract
The neurotrophic and neuroprotective potential of the α-melanocyte-stimulating hormone (α-MSH) analog cyclo-[Ac-Nle4,Asp5, -Phe7,Lys10]α-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 μg kg−1 per 48 h, s.c., but not at a dose of 2 or 50 μg 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 α-MSH analog melanotan-II in nerve regeneration and neuroprotection.