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

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。

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 meta-bolism.And the inhibition of CNS of R-ornidazole was stronger than that of S-ornidazole.Thus S-ornidazole is more suitable than R-ornidazole for clinical use.