期刊
NEUROPHARMACOLOGY
卷 53, 期 7, 页码 821-831出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2007.08.012
关键词
group I metabotropic glutamate receptor; MPEP; status epilepticus; neuroprotection
By intravenous administration of group I metabotropic glutamate receptor antagonists at I or 2 h during pilocarpine induced status epilepticus (PISE), we showed that mGluR 1 antagonists AIDA or LY367385 (at dosages ranging from 25 to 200 mg/kg), mGluR5 antagonists SIB1757 (at dosages ranging from 25 to 200 mg/kg), SIB 1893 (from 25 to 100 mg/kg), MPEP (from 25 to 100 mg/kg) injected at I or 2 h during PISE were ineffective in controlling status epilepticus (SE). However, when administered at I h during PISE, MPEP at 200 mg/kg, combination of MPEP (200 mg/kg) with MK801 (0.1 mg/kg) or with MK801 (0.1 mg/kg) and diazepam (0.5 mg/kg), combination of SIB 1893 (200 mg/kg) with MK801 (0.1 mg/kg) could effectively control behavioral SE, and were neuroprotective. In particular, the combination of MPEP with MK801 and diazepam could stop both behavioral SE and electrical SE (under EEG monitoring) within a few minutes after the administration. HPLC study showed that a high level of MPEP was maintained in the blood and its metabolism rate was slow in experimental mice with PlSE. We therefore concluded that the combination of MPEP (200 mg/kg) with MK801 (0.1 mg/kg) and diazepam (0.5 mg/kg) could effectively stop SE and its subsequent neuronal loss in the hippocampus when administered I h during PISE. It may provide a new approach to effectively control intractable SE. (c) 2007 Elsevier Ltd. All rights reserved.
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