Prevention of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic toxicity in mice by MDL 72145, a selective inhibitor of MAO-B |
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| Authors: | M V Kindt R E Heikkila |
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| Institution: | 1. Department of Psychology, Binghamton University, Binghamton, NY, USA;2. Barrow Neurological Institute, Phoenix, AZ, USA;1. Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, United States;2. Department of Biotechnology, American University of Ras Al Khaimah, United Arab Emirates;3. Wake Forest University Primate Center, Department of Pathology/Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States;4. Acetylon Pharmaceuticals, Inc., 70 Fargo St., Boston, MA 02210, United States;5. Edward Via College of Osteopathic Medicine, Blacksburg, VA 24060, United States |
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| Abstract: | Pretreatment of mice with the potent and selective monoamine oxidase B (MAO-B) inhibitor MDL 72145 ((E)-2-(3',4'-dimethoxyphenyl)-3-fluoroallylamine) protected against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice treated with MDL 72145 prior to MPTP did not exhibit the decrement in the neostriatal content of dopamine and its metabolites normally seen after MPTP administration. This observation adds further support to the concept that the oxidation of MPTP by MAO-B to its corresponding pyridinium analog, 1-methyl-4-phenylpyridinium (MPP+), is an important feature of the neurotoxic process. |
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