Talipexole protects dopaminergic neurons from methamphetamine toxicity in C57BL/6N mouse.
The effect of protection of dopaminergic neurons by talipexole, a dopamine (DA) agonist, is investigated on a methamphetamine (MA)-induced parkinsonism model of mice (C57BL/6N). The reduction of tyrosine hydroxylase activity in the striatum 72 h after MA (5 mg/kg every 2 h, four times) treatment was attenuated by the administration of talipexole (0.25 mg/kg or 1.0 mg/kg) prior to the administration of MA. In an in vitro experiment, talipexole inhibited the adduction reaction of hydroxyl radicals to salicylate. Taken together, these data suggest that the protective effect of talipexole on DA neurons is, in part, caused by the hydroxyl radical-scavenging action of the drug.
Kondo
T
T
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. tkondo@med.juntendo.ac.jp
Shimada
H
H
Hatori
K
K
Sugita
Y
Y
Mizuno
Y
Y
D000818:Animals; D001381:Azepines / Q000494:pharmacology* / Q000627:therapeutic use; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D004790:Enzyme Induction / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005841:Gentisates; D062385:Hydroxybenzoates / Q000032:analysis; D017665:Hydroxyl Radical / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000517:prevention & control*; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D012459:Salicylates / Q000378:metabolism; D020156:Salicylic Acid; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis*
D001381:Azepines; D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D016166:Free Radical Scavengers; D005841:Gentisates; D062385:Hydroxybenzoates; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D017448:Receptors, Dopamine D2; D012459:Salicylates; D017665:Hydroxyl Radical; D008694:Methamphetamine; C009135:2,3-dihydroxybenzoic acid; C024763:talipexole; D014446:Tyrosine 3-Monooxygenase; D020156:Salicylic Acid; C010925:2,5-dihydroxybenzoic acid; D004298:Dopamine