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奥硝唑对映体对小鼠中枢抑制作用研究

Different mechanism between ornidazole enantiomers on central nervous system in mice

  • 摘要: 探讨左旋和右旋奥硝唑静脉注射(iv)对小鼠中枢神经系统抑制作用的机制,以及奥硝唑光学对映体之间神经毒性的差异,为临床用药提供指导。左旋及右旋奥硝唑(40,60,80 mg/kg,iv)给药30 min后,用转棒实验测定小鼠运动协调能力,以评价药物对小鼠中枢抑制作用的强弱。测定并比较对小鼠给药30 min后全脑Na+,K+-ATP酶、Ca2+-ATP酶、琥珀酸脱氢酶(SDH)活性的影响。右旋奥硝唑可使小鼠呈现中枢抑制状态,影响其运动协调能力,并呈剂量相关性地抑制脑内Na+,K+-ATP酶、Ca2+-ATP酶、SDH活性。左旋奥硝唑组则均与对照组无显著性差异。右旋奥硝唑的中枢抑制作用可能与抑制脑内Na+,K+-ATP酶、Ca2+-ATP酶活性,抑制呼吸链关键酶SDH有关。

     

    Abstract: This study was designed to compare the differences in the neurotoxic effects between ornidazole enantiomers and to elucidate their underlying mechanisms,which will provide advice for a safer and more effective clinical use.15% propylene glycol solution,R- or S- ornidazole (40,60 and 80 mg/kg) was injected intravenously in different groups.Effects of the drugs on motor coordination were assayed by rotarod test,and activities of sodium-potassium ATPase (Na+,K+-ATPase),calcium ATPase (Ca2+-ATPase) and succinate dehydrogenase (SDH) were determined 30 min after administration.The time of mice walking on the rotarod in the R-ornidazole groups were longer than those in the S-ornidazole groups.A significant dose-dependent suppression of the activities of Na+,K+-ATPase,Ca2+-ATPase and SDH was discovered in R-ornidazole groups.However,S-ornidazole exhibited no significant dose-dependent suppression.The results indicated that the potential mechanism of CNS inhibition of ornidazole was mediated through the suppression of activities of the key enzymes of energy metabolism.And the inhibition of CNS of R-ornidazole was stronger than that of S- ornidazole.Thus S-ornidazole is more suitable thanR-ornidazole for clinical use.

     

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