Source:http://linkedlifedata.com/resource/pubmed/id/11169768
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| Predicate | Object |
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| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2001-2-22
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| pubmed:abstractText |
The neurotoxic potential of amphetamine and related drugs is well documented. However, methylphenidate, an amphetamine derivative used in the treatment of attention deficit hyperactivity disorder, and known to increase synaptic dopamine (DA) levels, seems to lack neurotoxic potential. It is hypothesized that both dopaminergic and serotonergic systems are involved in the neurotoxicity of amphetamine derivatives. The purpose of the present study was to evaluate the neurotoxic potential of methylphenidate and to test whether stimulation of the serotonergic system may confer neurotoxic properties to methylphenidate for DA or serotonin (5-HT) neurons. In addition, the present study was undertaken to evaluate the necessity to perform future SPECT studies in individuals using both methylphenidate and 5-HT-acting agents. We therefore measured monoaminergic transporters in rat brain using radioligands suitable for SPECT imaging ([123I]beta-CIT and [123I]FP-CIT). Groups of rats were treated with methylphenidate or saline for 4 days. Additional groups were treated with the selective 5-HT(2) receptor agonist quipazine or the selective 5-HT reuptake blocker fluoxetine, alone or in combination with methylphenidate. Binding studies were performed 5 days after the last treatment. In a second experiment, methylphenidate in combination with quipazine, along with a control group, was retested. In this experiment, monoaminergic terminal density was estimated 2 weeks (rather than 5 days) after drug treatment. Five days, but not 2 weeks, after treatment a significant reduction in specific [123I]FP-CIT binding was observed in the frontal cortex and hippocampus of rats treated with methylphenidate in combination with quipazine. These changes probably do not reflect neurotoxic changes of frontal cortex and hippocampal DA terminal markers, but a compensatory downregulation of DA transporters. These findings suggest potential harmful effects of concomitant use of drugs directly activating 5-HT2 receptors in patients using methylphenidate.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-carbomethoxy-8-(3-fluoropropyl)-3-...,
http://linkedlifedata.com/resource/pubmed/chemical/Biogenic Monoamines,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Plasma Membrane Transport...,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Uptake Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fluoxetine,
http://linkedlifedata.com/resource/pubmed/chemical/Iodine Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Methylphenidate,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Quipazine,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Uptake Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Tropanes
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
0887-4476
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2001 Wiley-Liss, Inc.
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| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
39
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
193-200
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:11169768-Animals,
pubmed-meshheading:11169768-Biogenic Monoamines,
pubmed-meshheading:11169768-Carrier Proteins,
pubmed-meshheading:11169768-Dopamine,
pubmed-meshheading:11169768-Dopamine Plasma Membrane Transport Proteins,
pubmed-meshheading:11169768-Dopamine Uptake Inhibitors,
pubmed-meshheading:11169768-Fluoxetine,
pubmed-meshheading:11169768-Hippocampus,
pubmed-meshheading:11169768-Iodine Radioisotopes,
pubmed-meshheading:11169768-Male,
pubmed-meshheading:11169768-Membrane Glycoproteins,
pubmed-meshheading:11169768-Membrane Transport Proteins,
pubmed-meshheading:11169768-Methylphenidate,
pubmed-meshheading:11169768-Nerve Tissue Proteins,
pubmed-meshheading:11169768-Neurons,
pubmed-meshheading:11169768-Prefrontal Cortex,
pubmed-meshheading:11169768-Quipazine,
pubmed-meshheading:11169768-Rats,
pubmed-meshheading:11169768-Rats, Wistar,
pubmed-meshheading:11169768-Serotonin Receptor Agonists,
pubmed-meshheading:11169768-Serotonin Uptake Inhibitors,
pubmed-meshheading:11169768-Tropanes
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| pubmed:year |
2001
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| pubmed:articleTitle |
Addition of a 5-HT receptor agonist to methylphenidate potentiates the reduction of [123I]FP-CIT binding to dopamine transporters in rat frontal cortex and hippocampus.
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| pubmed:affiliation |
Graduate School of Neurosciences, Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands. l.reneman@amc.uva.nl
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| pubmed:publicationType |
Journal Article
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