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Capillary Electrophoresis-Mass Spectrometry-Based Detection of Drugs and Neurotransmitters in Drosophila Brain

Artikel i vetenskaplig tidskrift
Författare Nhu TN Phan
Jörg Hanrieder
Carina Berglund
Andrew G Ewing
Publicerad i Analytical Chemistry
Volym 85
Nummer/häfte 17
Sidor 8448-8454
ISSN 0003-2700
Publiceringsår 2013
Publicerad vid Institutionen för kemi och molekylärbiologi
Sidor 8448-8454
Språk en
Länkar dx.doi.org/10.1021/ac401920v
Ämnesord transporter knockout mice, biogenic-amine levels, dopamine-transporter, methylphenidate, cocaine, stress, pharmacokinetics, melanogaster, abuse, methamphetamine
Ämneskategorier Kemi

Sammanfattning

Capillary electrophoresis coupled to mass spectrometry has been used to determine the in vivo concentrations of the neuroactive drug, methylphenidate, and a metabolite in, the heads of the fruit fly, Drosophila melanogaster. These concentrations, evaluated at the site of action, the brain, have been correlated with orally administrated methylphenidate. D. melanogaster has a relatively simple nervous system but possesses high-order brain functions similar to humans; thus, it has been used as a common model system in biological and genetics research. Methylphenidate has been used to mediate cocaine addiction due to its lower pharmacokinetics, which results in fewer addictive and reinforcing effects than cocaine; the effects of the drug on the nervous system, however, have not been fully understood. In addition to measurements of drug concentration, the method has been used to examine drug-dose dependence on the levels of several primary biogenic amines. Higher in vivo concentration of methylphenidate is observed with increasing feeding doses up to 25 mM methylphenidate. Furthermore, administrated methylphenidate increases the drug metabolism activity and the neurotransmitter levels; however, this increase appears to saturate at a feeding dose of 20 mM. The method developed for the fruit fly provides a new tool to evaluate the concentration of administered drug at the site of action and provides information concerning the effect of methylphenidate on the nervous system.

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