title: Efficacy of the neuropeptide ORG.2766 in the prevention and treatment of cisplatin-induced neurotoxicity in rats.
abstract: In rats chronic systemic treatment with cisplatin results in a sensory neuropathy as evidenced by a reduction in the sensory conduction velocity in the sciatic nerve. Concomitant administration of the neurotrophic ACTH4-9 analog, ORG.2766, prevents the occurrence of the neuropathy. In addition, treatment with ORG.2766 stops further deterioration and improves recovery of an already established cisplatin-induced neuropathy. Furthermore, concomitant administration of ORG.2766 during a first cisplatin treatment period results in a better resistance against neurotoxicity in a second exposure period. Finally, ORG.2766 was shown not to hamper the anti-tumor effect of cisplatin in mice, carrying implanted tumor cells from a FMa human tumor line. These data are discussed in view of the potential clinical use of ORG.2766 in prevention and treatment of cisplatin-induced neuropathy.
authors.affiliation: Division of Molecular Neurobiology, Rudolf Magnus Institute for Pharmacology, University of Utrecht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Gerritsen van der Hoop
authors.forename: P
authors.initials: P
authors.lastname: de Koning
authors.forename: E
authors.initials: E
authors.lastname: Boven
authors.forename: J P
authors.initials: JP
authors.lastname: Neijt
authors.forename: F G
authors.initials: FG
authors.lastname: Jennekens
authors.forename: W H
authors.initials: WH
authors.lastname: Gispen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002945:Cisplatin / Q000009:adverse effects*; D005260:Female; D051379:Mice; D008819:Mice, Nude; D009046:Motor Neurons / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects*; D010446:Peptide Fragments / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D010446:Peptide Fragments; C013765:Org 2766; D000324:Adrenocorticotropic Hormone; D002945:Cisplatin