Neurotoxicity of levodopa on catecholamine-rich neurons.
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.
Mena
M A
MA
Departamento de Investigación, Centro Ramón y Cajal, Madrid, Spain.
Pardo
B
B
Casarejos
M J
MJ
Fahn
S
S
García de Yébenes
J
J
D002395:Catecholamines / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007980:Levodopa / Q000493:pharmacokinetics / Q000633:toxicity*; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D012642:Selegiline / Q000494:pharmacology
D002395:Catecholamines; D012642:Selegiline; D007980:Levodopa; D004298:Dopamine