Different mechanism between ornidazole enantiomers on central nervous system in mice

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.