Effects of the Ornidazole (cas 16773-42-5) enantiomers on the central nervous system: Involvement of the GABAA receptor
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Add time:07/20/2019 Source:sciencedirect.com
This is the preliminary study of the sedative and muscle relaxation activity of Ornidazole (cas 16773-42-5) enantiomers, which are widely used in the treatment of susceptible protozoal infections and anaerobic bacterial infections. Adverse effects on the central nervous system (CNS) are the main side effects of ornidazole during its clinical application. The aim of this study was to compare the different central inhibitory effects between S-(−) ornidazole and R-(+) ornidazole in mice and clarify the possible mechanisms. In the present study, central effects of ornidazole were evaluated by open-field test and rota-rod test, and such effects were reversed by pre-treatment with flumazenil (i.p., 10 mg/kg) suggesting that ornidazole exhibits such action by interacting with the GABAergic system. Then, the functional difference between S-(−) ornidazole and R-(+) ornidazole was further explored by evaluating the contents of glutamate (Glu) and γ-aminobutyric acid (GABA) in the brain, and Western blot was used to measure glutamic acid decarboxylase (GAD65/67) expression in the mice cerebral cortex. We found that R-(+) ornidazole mediated an increase in GABA level while decreased the level of glutamate through upregulation of GAD65/67 in the cerebral cortex. Taken together, our study suggests that R-(+) ornidazole mediate stronger central inhibitory effects than S-(−) ornidazole through interaction with the GABAergic system.
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