Aoyama T, Kotaki H, Sawada Y, Iga T
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, Japan.
Pharm Res. 1994 Mar;11(3):407-11. doi: 10.1023/a:1018917205292.
To investigate the stereoselective distribution of methylphenidate (MPD) enantiomers in rats, the concentrations of each enantiomer were determined in plasma and brain regions (cerebellum, striatum, basal forebrain, brain stem, and cortex) after iv administration of racemic MPD and its individual enantiomers. The concentrations of MPD enantiomers in each brain region reached pseudo-steady state within 10 min after iv administration of racemic MPD (2 mg/kg dose). The influx clearances for MPD calculated from Kpapp values in each brain region were not significantly different between MPD enantiomers and between the five brain regions. The mean Kpapp values for (+)-MPD in the striatum at 120 and 240 min after administration of racemic MPD were 10.1 and 10.5, respectively, and these values at each time were significantly larger than the Kpapp values (7.5 and 7.0, respectively) for the (-)-isomer (P < 0.01). The Kpapp value for (+)-MPD in the striatum decreased by coadministration of mazindol as an inhibition of both dopamine and norepinephrine reuptake, but it was not changed by desipramine as a norepinephrine reuptake inhibitor. These results suggest that (+)-MPD was bound specifically to the dopamine reuptake site in the striatum.
为研究哌甲酯（MPD）对映体在大鼠体内的立体选择性分布，在静脉注射消旋MPD及其单个对映体后，测定了血浆和脑区（小脑、纹状体、基底前脑、脑干和皮质）中各对映体的浓度。静脉注射消旋MPD（剂量为2mg/kg）后10分钟内，各脑区MPD对映体的浓度达到假稳态。根据各脑区的Kpapp值计算得到的MPD流入清除率，在MPD对映体之间以及五个脑区之间均无显著差异。静脉注射消旋MPD后120分钟和240分钟时，纹状体中（+）-MPD的平均Kpapp值分别为10.1和10.5，且每次这些值均显著大于（-）-异构体的Kpapp值（分别为7.5和7.0）（P<0.01）。作为多巴胺和去甲肾上腺素再摄取抑制剂的吗茚酮共同给药后，纹状体中（+）-MPD的Kpapp值降低，但作为去甲肾上腺素再摄取抑制剂的地昔帕明给药后，该值未发生变化。这些结果表明，（+）-MPD特异性结合于纹状体中的多巴胺再摄取位点。
