Movement Disorders · 1992 · 139 citations · 29 references
MedicineNeurosciencePharmacologyCellular NeurobiologyNeurochemistryNeuropharmacologyDrug-induced NeurotoxicityMonoamine NeurochemistryNeurodegeneration MechanismsNeuroprotectionNeurotoxic MechanismsNeurotoxicity MechanismsMonoamine Oxidase InhibitionMonoamine Oxidase InhibitorsMonoamine Oxidase InvolvementNeuroblastoma BiologyNeurotoxicityQuinone FormationQuinone MetabolismTryptophan Metabolism
The human neuroblastoma cells NB69 are a catecholamine-rich cell line with pharmacological properties similar to dopamine neurons. This cell line was used to study the neurotoxicity of levodopa on catecholamine neurons. Levodopa, at 50 x 10(-6) M or higher concentrations, produced a dose- and time-dependent reduction in the number of live cells, [3H]thymidine uptake, levels of protein and DNA, and an enhancement of the quinone formation. This is a specific effect of levodopa since it did not happen in NB69 cells incubated with equimolar concentrations of leucine and tryptophan. Treatment with deprenyl, an inhibitor of monoamine oxidase type B, partially prevented levodopa neurotoxicity, suggesting that the mechanism of toxicity was, at least in part, related to an increase in the metabolism of dopamine catalyzed by monoamine oxidase.
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Chronic Parkinsonism in Humans Due to a Product of Meperidine-Analog Synthesis
J. William Langston, Philip L. Ballard, James W. Tetrud et al. · Science · 1983 · 4.9K citations
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Medicine, Neurology, Neuroscience +12
Doyle G. Graham, S M Tiffany, William R. Bell et al. · Molecular Pharmacology · 1978 · 956 citations