反式曲马多及氧去甲基曲马多对映体跨血脑屏障转运

TRANSPORTATION OF THE ENANTIOMERS OF TRANS TRAMADOL AND O-DEMETHYLTRAMADOL ACROSS BLOOD-BRAIN BARRIER

目的 研究反式曲马多 (transT)及其活性代谢物氧去甲基曲马多 (M1 )对映体的跨血脑屏障转运。方法大鼠ip盐酸transT (16 7mg·kg- 1 或 5 0mg·kg- 1 ) 1h后取血、脑脊液和大脑皮层 ,高效毛细管电泳测定血清、脑脊液和大脑皮层中transT和M1 对映体的浓度。结果 TransT和M1 各对映体浓度以大脑皮层中最高 ,血清中浓度居中 ,脑脊液中浓度最低。在血清中 ,(+) transT的浓度明显高于 (- ) transT的浓度 ,M1 两对映体的浓度无明显区别 ;在脑脊液和大脑皮层中 ,(+) transT的浓度明显高于 (- ) transT的浓度 ,(+) M1 的浓度明显低于 (- ) M1 的浓度。结论 TransT和M1 的跨血脑屏障转运具有立体选择性 ,脑组织中分别以 (+) 对映体和 (- ) 对映体浓度较高。

AIM To investigate the transportation of the enantiomers of trans tramadol ( trans T) and its active metabolite, O -demethyltramadol (M 1) across blood-brain barrier. METHODS Rats were sacrificed by femoral artery bleeding 1 h after ip administration of trans T hydrochloride, 16 7 mg·kg -1 or 50 0 mg·kg -1 . Blood, cerebrospinal fluid and cerebral cortex were taken out. The enantiomers of trans T and M 1 were analyzed by high performance capillary electrophoresis (HPCE). RESULTS Among the three tissues, the concentration of each enantiomer of trans T and M 1 was the highest in the cerebral cortex, and the lowest in the cerebrospinal fluid. In the serum, the concentration of (+)- trans T was higher than that of (-)- trans T, and the concentrations of the enantiomers of M 1 were similar. In the cerebrospinal fluid and cerebral cortex, the concentration of (+)- trans T was higher than that of (-)- trans T, and the concentrations of (+)-M 1 was lower than that of (-)-M 1. CONCLUSION The transportation across blood-brain barrier of the enantiomers of trans T and M 1 was stereoselective. In the brain tissues, the concentrations of (+)- trans T and (-)-M 1 were higher than those of their enantiomers.