title: Tricyclic Antidepressants Amitriptyline and Desipramine Induced Neurotoxicity Associated with Parkinson's Disease.
abstract: Recent studies report that a history of antidepressant use is strongly correlated with the occurrence of Parkinson's disease (PD). However, it remains unclear whether antidepressant use can be a causative factor for PD. In the present study, we examined whether tricyclic antidepressants amitriptyline and desipramine can induce dopaminergic cell damage, both in vitro and in vivo. We found that amitriptyline and desipramine induced mitochondria-mediated neurotoxicity and oxidative stress in SH-SY5Y cells. When injected into mice on a subchronic schedule, amitriptyline induced movement deficits in the pole test, which is known to detect nigrostriatal dysfunction. In addition, the number of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta was reduced in amitriptyline-injected mice. Our results suggest that amitriptyline and desipramine may induce PD-associated neurotoxicity.
authors.affiliation: Department of Molecular Biology, Sejong University, Seoul 143-747, Korea.
authors.forename: Min-yeong
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Department of Molecular Biology, Sejong University, Seoul 143-747, Korea.
authors.forename: Seokheon
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Biology, Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Nahmhee
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Biology, Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Ki Soon
authors.initials: KS
authors.lastname: Shin
authors.affiliation: Department of Molecular Biology, Sejong University, Seoul 143-747, Korea.
authors.forename: Shin Jung
authors.initials: SJ
authors.lastname: Kang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000639:Amitriptyline / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003891:Desipramine / Q000494:pharmacology* / Q000633:toxicity; D059290:Dopaminergic Neurons / Q000187:drug effects*; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects; D010300:Parkinson Disease / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000975:Antioxidants; D017382:Reactive Oxygen Species; D000639:Amitriptyline; D000255:Adenosine Triphosphate; D003891:Desipramine
keywords: Parkinson’s disease; amitriptyline; desipramine; neurotoxicity; tricyclic antidepressant