title: Effect of N1-dansylspermine and Ro25,6981 on locomotor activity in naive mice and in the reserpinized mouse model of Parkinson's disease.
abstract: The effect of N1-dansylspermine, a polyamine analogue and competitive polyamine antagonist, and Ro25,6981, a noncompetitive polyamine antagonist with good affinity and selectivity for the GluN2B subunit, on locomotor activity in naive mice was investigated. Furthermore, the ability of the polyamine antagonists to reverse reserpine-induced hypokinesia was assessed, 24 h after injection of a catecholamine-depleting dose of reserpine (5 mg/kg, subcutaneous), to investigate the therapeutic potential of polyamine antagonists in Parkinson's disease. N1-dansylspermine significantly decreased locomotor activity in naive animals (P<0.001) but caused a mild, but significant increase in locomotor activity in reserpinized mice at the highest dose tested (P<0.05). Ro25,6981 significantly stimulated locomotor activity in naive animals (P<0.001) and had a slight significant stimulatory effect on reserpine-induced hypokinesia (P=0.05). N1-dansylspermine and Ro25,6981 had opposite effects on locomotor activity in naive mice, but both had a mild antiparkinsonian effect in the reserpine model. These findings suggest that antagonism of the polyamine binding site on the GluN2B subunit can reduce hypokinesia, albeit to a limited extent.
authors.affiliation: Department of Biosciences, University of Hertfordshire, Hatfield, UK.
authors.forename: Carol
authors.initials: C
authors.lastname: Devadasan
authors.forename: Beryl
authors.initials: B
authors.lastname: Starr
authors.forename: Karen M
authors.initials: KM
authors.lastname: Doyle
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000633:toxicity; D003619:Dansyl Compounds / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology; D010636:Phenols / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D012110:Reserpine / Q000633:toxicity
chemical_list: D000978:Antiparkinson Agents; D014150:Antipsychotic Agents; D003619:Dansyl Compounds; D010636:Phenols; D010880:Piperidines; C109643:Ro 25-6981; C001026:5-dimethylaminonaphthalene-1-sulfonamide; D012110:Reserpine