Rational Combination Of Extractions Of Antiepileptic Chinese Herbs In Experimental Research

Objective To compare the anticonvulsant action of various combinations of four extractions of chinese hers, find the best combination and its combinative dose ratio and explore its mechanism. Methods Maximal electroshock seizure (MES), Metrazol seizure test (MET) was used respectively to compare the anticonvulsant rate and seizure latency of eleven compounds. Anticonvulsant effect and toxic-effect of the best combination, at three fixed ratios of 1:4, 1:1, 4:1 were evaluated with isobolographic analysis, which allowed the determination of synergistic,additive and antagonistic. Pharmacodynamic Parameters of combinations of different dose ratios (1:0, 0:1,1:1, 4:1,1:4) were assayed with Pharmacological Effective Method . Using the model of seizure rats induced by penicillin localized injected in cortex, compare the effect of the optimal combination with single extraction on seizure latency, frequency of epileptiform discharge, highest wave of hippocampus and cortex EEG, the changes of convulsant behaviors. The neurotransmitters content in brain related to epilepsy were determined by high performance liquid chromatography (HPLC) in order to compare the effect of combinations with single extraction on the level of Glu, Asp, Gly and GABA of hippocampus. Results and conclusions (1)Among eleven compounds,except for RB+RAT, all the others could antagonized MES in mice, the anticonvulsant rate of PT+UN and PT+UN+RB+RAT are the highest, attaining 60%; PT+UN, PT+UN+RAT and PT+UN+RAT+RB, the three compounds could significantly prolong latent periods on MET in mice. (2) Combinations of PT and UN, at the fixed ratios of 4:1, were additive in the MES test and simultaneously antagonistic in the acute toxic test, showing the best profile for AED combinations. In contrast, the ratios of 1:4, were purely additive, either as regards the anticonvulsant activity against MES or in terms of toxicity , resulting in unfavorable AED combination. While at the ratio of 1:1, despite synergistic in the MES test ,were additive in acute toxic test. (3) The two drugs alone and three fixed-ratio combinations could dose-dependently antagonize MES in mice. Except for the 4:1 group,the minimal effective dosage of combinative groups are lower than the single drug. All these groups can produce effect at 30 minutes after administration and attain the peak at 1 hour and can persist for about 4 hour. All belong to short-half period compounds.(4)The 4:1 combination and two drugs alone could inhibit convulsant behaviors and epileptiform discharge.The combination is better than two drugs alone in prolonging the seizure latency and epileptiform discharge latency, but has no significantly difference in reducing the frequency of epileptiform discharge and decreasing the highest wave of EEG..It can effectively antagonize the pencillin-induced seizure.Meanwhile,it can significantly decrease the Glu level and increase the GABA level.The GABA level in the 4:1 combination is higher than the two drugs alone .The anticonvulsant mechanism of combination might relate to decreasing the excitability of Glutamic acid neuron and increasing the inhibility of GABA neuron altogether.