Department of Chemistry and Molecular Biology, University of Gothenburg, Kemivägen 10, SE-412 96 Gothenburg, Sweden.
Anal Chem. 2013 Sep 3;85(17):8448-54. doi: 10.1021/ac401920v. Epub 2013 Aug 19.
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.
毛细管电泳-质谱联用技术已被用于测定活体果蝇头部神经活性药物哌醋甲酯及其代谢物的浓度。这些在作用部位(大脑)评估的浓度与口服给予的哌醋甲酯相关联。果蝇的神经系统相对简单,但具有与人类相似的高级脑功能;因此,它已被用作生物学和遗传学研究中的常见模型系统。由于哌醋甲酯的药代动力学较低,导致成瘾性和强化作用比可卡因少,因此已被用于治疗可卡因成瘾;然而,该药物对神经系统的影响尚未完全了解。除了药物浓度的测量外,该方法还用于研究几种主要生物胺的药物剂量依赖性。随着 25mM 哌醋甲酯喂养剂量的增加,体内哌醋甲酯的浓度更高。此外,给予的哌醋甲酯增加了药物代谢活性和神经递质水平;然而,这种增加似乎在 20mM 的喂养剂量下达到饱和。为果蝇开发的方法提供了一种新的工具,可用于评估作用部位给予药物的浓度,并提供有关哌醋甲酯对神经系统影响的信息。