Threo-methylphenidate hydrochloride is a catecholamine reuptake inhibitor that inhibits dopamine transporter (DAT) and norepinephrine transporter (NET)[1]. Threo-methylphenidate hydrochloride is used to treat attention deficit hyperactivity disorder (ADHD)[2]. Threo-methylphenidate hydrochloride has central nervous system excitability and sympathomimetic effects, and can also affect the cardiovascular system[3].
In vitro, when glial cells were treated with Threo-methylphenidate hydrochloride (100µM, 30 min), a significant increase in [3H]-D-Asp was detected after 2 hours, and this effect persisted after 12hours[4]. The concentration range of Threo-methylphenidate hydrochloride that inhibits NET in HEK293 cells is 0.04-0.42µM, and the concentration range that inhibits DAT is 0.08-0.34µM[5].
In vivo, Threo-methylphenidate hydrochloride(30mg/kg) caused a shortening of the QT interval in the electrocardiogram of beagle dogs and an increase in blood pressure[3]. Threo-methylphenidate hydrochloride(10mg/kg, o.p.) may reduce urine flow and glomerular filtration rate in Wistar rats, but has no harmful effect on renal tubules[6].Threo-methylphenidate hydrochloride(4 mg/kg) increased the anticipatory response of zebrafish in a 5-choice series response task and also increased the overall activity level of the experimental group [7].
References:
Markowitz J S , Patrick K S. Differential Pharmacokinetics and Pharmacodynamics of Methylphenidate Enantiomers[J]. Journal of Clinical Psychopharmacology, 2008, 28: 54-61.
[2]Heal D J , Pierce D M .Methylphenidate and its Isomers: Their Role in the Treatment of Attention-Deficit Hyperactivity Disorder Using a Transdermal Delivery System[J].Cns Drugs, 2006, 20(9):713-738.
[3]Wakamatsu A , Nomura S , Tate Y ,et al. Effects of methylphenidate hydrochloride on the cardiovascular system in vivo and in vitro: A safety pharmacology study[J].Journal of Pharmacological & Toxicological Methods, 2009, 59(3):128-134.
[4]A M. Guillem, Z Martı´nez-Lozada, L C. Herna´ndez-Kell, et al. Methylphenidate Increases Glutamate Uptake in Bergmann Glial Cells[J]. Neurochem Res. 2015(40):2317-2324.
[5]Luethi, D.K., Philine J.Brandt, Simon D. K, et al. Pharmacological profile of methylphenidate-based designer drugs[J].Neuropharmacology, 2018, 134.
[6]Luiza Herbene Macedo Soares Salviano,et al. Study of the safety of methylphenidate: Focus on nephrotoxicity aspects[J].Life Sciences. 2015:137-142.
[7]Parker M O , Brock A J , Sudwarts A ,et al.Atomoxetine reduces anticipatory responding in a 5-choice serial reaction time task for adult zebrafish[J].Psychopharmacology, 2014, 231(13):2671.
盐酸苏哌甲酯(Threo-methylphenidate hydrochloride)是一种儿茶酚胺再摄取抑制剂,抑制多巴胺转运蛋白(DAT)和去甲肾上腺素转运蛋白(NET)[1]。盐酸苏哌甲酯用于治疗注意力缺陷多动障碍(ADHD)[2]。盐酸苏哌甲酯具有中枢神经系统兴奋和拟交感神经作用,还可影响心血管系统[3]。
在体外,盐酸苏哌甲酯(100 µM,30min)处理神经胶质细胞,2小时后检测到[3H]-D-Asp显著增加,并且该作用在12小时后仍然存在[4]。盐酸苏哌甲酯在HEK293细胞中抑制NET的浓度范围为0.04-0.42 µM,抑制DAT 的浓度范围为0.08-0.34 µM[5]。
在体内,盐酸苏哌甲酯(30mg/kg)导致比格犬心电图的QT间期缩短,出现血压升高[3]。盐酸苏哌甲酯(10mg/kg, o.p.)可能会降低Wistar大鼠尿流量和肾小球滤过率,对肾小管没有危害作用[6]。盐酸苏哌甲酯(4 mg/kg)增加了斑马鱼在5选择系列反应任务中的预期反应,还使实验组的总体活动水平增加[7]。