Seizure Threshold. Midazolam Rectally Part Of The Pharmacokinetics Of Its Anti-rat Cortical And Hippocampal Pathological Changes Observed,

Objective: Our objective is to study absorption condition in short time whenMidazolam is administered by rectum and whether it has the quicklyanticonvulsive effect and the protective function for neuron shape and structuresof hippocampus in the rat, which may can provide evidence for clinicalmedication. Method: (1) We adopted high performance liquid chromatography toexamine concentration of Midazolam in human serum and observe its conditionand rate of absorption in rectum..(2) We used the threshold for localized seizureby direct cortical stimulation model to observe the influence of Midazolam andDiazepam on convulsant threshold by rectum in few minutes and study theirchanges of seasoning and effect. (3) After two weeks, we observed the shapeand structures of hippocampus by HE staining. Result: (1) Midazolam was absorbed quickly by rectum and itsconcentration could be examined after one minutes .The drug was safe and therewas no inhibitive phenomenon of cardiovascular system and respirationsystem.(2)Both Midazolam and Diazepam could elevate the convulsantthreshold of the rats(P<0.05).But the anticonvulsive effect in the group ofMidazolam was more powerful than in the group of Diazepam at identical timepoint. (3)The time of arriving the top convulsant threshold rose by administeringMidazolam was 5 minutes while it was 8 minutes after administeringDiazepam.,so Midazolam could play the more fully anticonvulsion role. (4)Theneuron cell of hippocampus was harmed more seriously in control group.The main damage were pyramidal cell structures were disperative replication, celldecreased and deformed,karyopyknosis,nisslbody disappeared andschillerization neuron.;The condition in the group of Diazepam was better thanin the control group and the main damage was cell population decreased,endochylema had uniform pigmentosus pathological change. The condition inthe group of Midazolam was the best:the structures of pyramidal cell inhippocampus were relative regularity ,several cells had degeneration andnecrosis was not distinguished.The experiment exhibited that Midazolam hasprotective function for neuron of hippocampus, which is better than Diazepam. Conclusion: (1)Midazolam had the evident anticonvulsive effect and hadprotecting hippocampus neuron function when it was administered per rectum,whose function was more powerful than Diazepam. (2)Midazolam producequickly anticonvulsion effect by rectum within a few minutes. (3)Midazolamcould be absorpted effectively which was relatively safe and had no obviouslynegative action. (4)Midazolam would provide a new route of administeringfor acute convulsion seizure,which would be worth investigating infuture.