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Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate

Methylphenidate is a psychostimulant that inhibits the neuronal dopamine transporter. In addition, methylphenidate has the intriguing ability to provide neuroprotection from the neurotoxic effects of methamphetamine and perhaps also Parkinson’s disease; both of which may likely involve the abnormal...

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Autor principal: Volz, T.J
Formato: Texto
Lenguaje:English
Publicado: Bentham Science Publishers Ltd. 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701286/
https://www.ncbi.nlm.nih.gov/pubmed/19587858
http://dx.doi.org/10.2174/157015908787386041
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author Volz, T.J
author_facet Volz, T.J
author_sort Volz, T.J
collection PubMed
description Methylphenidate is a psychostimulant that inhibits the neuronal dopamine transporter. In addition, methylphenidate has the intriguing ability to provide neuroprotection from the neurotoxic effects of methamphetamine and perhaps also Parkinson’s disease; both of which may likely involve the abnormal accumulation of cytoplasmic dopamine inside dopaminergic neurons and the resulting formation of dopamine-associated reactive oxygen species. As delineated in this review, the neuroprotective effects of methylphenidate are due, at least in part, to its ability to attenuate or prevent this abnormal cytoplasmic dopamine accumulation through several possible neuropharmacological mechanisms. These may include 1) direct interactions between methylphenidate and the neuronal dopamine transporter which may attenuate or prevent the entry of methamphetamine into dopaminergic neurons and may also decrease the synthesis of cytoplasmic dopamine through a D2 receptor-mediated signal cascade process, and 2) indirect effects upon the functioning of the vesicular monoamine transporter-2 which may increase vesicular dopamine sequestration through both vesicle trafficking and the kinetic upregulation of the vesicular monoamine transporter-2 protein. Understanding these neuropharmacological mechanisms of methylphenidate neuroprotection may provide important insights into the physiologic regulation of dopaminergic systems as well as the pathophysiology of a variety of disorders involving abnormal dopamine disposition ranging from substance abuse to neurodegenerative diseases such as Parkinson’s disease.
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spelling pubmed-27012862009-07-08 Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate Volz, T.J Curr Neuropharmacol Article Methylphenidate is a psychostimulant that inhibits the neuronal dopamine transporter. In addition, methylphenidate has the intriguing ability to provide neuroprotection from the neurotoxic effects of methamphetamine and perhaps also Parkinson’s disease; both of which may likely involve the abnormal accumulation of cytoplasmic dopamine inside dopaminergic neurons and the resulting formation of dopamine-associated reactive oxygen species. As delineated in this review, the neuroprotective effects of methylphenidate are due, at least in part, to its ability to attenuate or prevent this abnormal cytoplasmic dopamine accumulation through several possible neuropharmacological mechanisms. These may include 1) direct interactions between methylphenidate and the neuronal dopamine transporter which may attenuate or prevent the entry of methamphetamine into dopaminergic neurons and may also decrease the synthesis of cytoplasmic dopamine through a D2 receptor-mediated signal cascade process, and 2) indirect effects upon the functioning of the vesicular monoamine transporter-2 which may increase vesicular dopamine sequestration through both vesicle trafficking and the kinetic upregulation of the vesicular monoamine transporter-2 protein. Understanding these neuropharmacological mechanisms of methylphenidate neuroprotection may provide important insights into the physiologic regulation of dopaminergic systems as well as the pathophysiology of a variety of disorders involving abnormal dopamine disposition ranging from substance abuse to neurodegenerative diseases such as Parkinson’s disease. Bentham Science Publishers Ltd. 2008-12 /pmc/articles/PMC2701286/ /pubmed/19587858 http://dx.doi.org/10.2174/157015908787386041 Text en ©2008 Bentham Science Publishers Ltd. http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Volz, T.J
Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate
title Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate
title_full Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate
title_fullStr Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate
title_full_unstemmed Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate
title_short Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate
title_sort neuropharmacological mechanisms underlying the neuroprotective effects of methylphenidate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701286/
https://www.ncbi.nlm.nih.gov/pubmed/19587858
http://dx.doi.org/10.2174/157015908787386041
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