Methylphenidate exerts no neurotoxic, but neuroprotective effects in vitro
First Online: 01 June 2006 Received: 15 February 2006 Accepted: 13 March 2006 DOI:
10.1007/s00702-006-0487-5 Cite this article as: Ludolph, A., Schaz, U., Storch, A. et al. J Neural Transm (2006) 113: 1927. doi:10.1007/s00702-006-0487-5 Summary.
Methylphenidate (MPH) is the most common used drug in child and adolescent psychiatry. Despite of this fact, however, little is known about its exact pharmacological mechanisms.
Here we investigated the toxic effects of MPH
in vitro in human embryonic kidney (HEK-293) cells stably expressing the human dopamine transporter (HEK-hDAT cells) and in cultured rat embryonic (E14.5) mesencephalic cultures. MPH alone (up to 1 mM) affected neither the growth of HEK-hDAT cells nor the survival of dopaminergic (DA) neurons in primary cultures after treatment up to 72 h. No differences in neuronal arborisation or in the density of synapses were detected. 1-methyl-4-phenylpyridinium (MPP +) showed no toxic effect in HEK-293 cells, but had significant toxic effects in HEK-hDAT cells and DA neurons. MPH (1 µM – 1 mM) dose-dependently reduced this cytotoxicity in HEK-hDAT cells and primary mesencephalic DA neurons.
The presented results show that application of MPH alone does not have any toxic effect on DA cells
in vitro. The neurotoxic effects of MPP + could be significantly reduced by co-application of MPH, an effect that is most likely explained by MPH blocking the DAT. Keywords: Methylphenidate, toxicity, neuroprotection, MPP +, in vitro study, mesencephalic neurons, dopaminergic system
The first and second authors contributed equally to this work
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