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The Study Of Effect Of Ketamine On Kindled Models

Posted on:2005-12-27Degree:MasterType:Thesis
Country:ChinaCandidate:J G ZhangFull Text:PDF
GTID:2144360152998743Subject:Pharmacology
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Ketamine is a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptor. It has been known that epileptic seizure is related to enhence of NMDA receptor. However, few papers about the effect of ketamine on kindled models has been seen in Chinese magazines.Objective: To investigate the antiepileptic effect of ketamine on kinded models in rats and to study the mechanism of ketamine on amygdala kindling in rats.Methods: To establish amygdala kindling models and lidocaine-induced chemical kindled models in rats and observe the effect of ketamine on kindled models and its combination with nicadipine at ineffective dose respectively. The influence of ketamine on the maximum electrical convulsions in mice and convusions induced by lithium chloride-pilocarpine nitrate were also observed.Results: Ketamine (10.0-30.0 mg.kg~-1, ip) dose-dependently inhibited the amygdala kindled seizure, shortened the afterdischarge duration (ADD) and reduced the Racine's stage (P<0.05). The combination of ketamine with nicardipine at ineffective dose shortened ADD and reduced Racine's stages (P<0.05). Ketamine(20.0-30.0mg.kg~-1, ip) significantly reduced the Racine's stage and reduce the rate of Racine's stage V grade on chemical kindled models induced by lidocaine (P<0.05) .Ketamine(10.0-20.0mg.kg~-1, ip) prolonged the latency and reduced the time of seizure on convusions induced by lithium chloride-pilocarpine nitrate(P<0.05). Ketamine(20.0-40.0mg.kg~-1, ip) can increase the latent period of seizured mice, significantly inhibit the time of seizure in MES experiment (P<0.05).Conclusion: Ketamine inhibits the seizure of the amygdala kindled and chemical kindled models induced by lidocaine. The combination with nicadipine suggest that the inhibition mechanism of ketamine is related to the blockade of the calcium channels of NMDA receptor.
Keywords/Search Tags:Ketamine, NMDA receptor, kindling, epilepsy, nicardipine
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