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.
Ter Laak
Mariël P
MP
Department of Medical Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
Brakkee
Jan H
JH
Adan
Roger A H
RA
Hamers
Frank P T
FP
Gispen
Willem Hendrik
WH
D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage; D005528:Foot / Q000294:innervation; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D017933:Peripheral Nervous System / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018043:Receptors, Corticotropin / Q000819:agonists*; D044101:Receptors, Melanocortin; D012018:Reflex / Q000187:drug effects; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology; D020426:Sciatic Neuropathy / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000494:pharmacology*
D018696:Neuroprotective Agents; D010456:Peptides, Cyclic; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C079282:melanotan-II; D000521:alpha-MSH; D002945:Cisplatin