The Study Of Anticonvulsant Effect Of The Combinations Of Carbamazepine,Valproate And Compounds Of Extracted By Pyruvate From Stellera Chamaejasme L In Chinese Herbal Medicine

Recently,Dr Liu Yuxi etal. from department of epilepsy in Shanxi Medical University found that stellera chamaejasme had strong anticonvulsant activity. It's spectrum of anticonvulsant activity was extensive, it's toxicity was low,so stellera chamaejasme was a potent and safe new antiepileptic herb. This experiment further studied the anticonvulsant activity of the combinations of carbamazepine(CBZ),valproate(VPA),and compounds of extracted by pyruvate from stellera chamaejasme L(CEPSC),and analyzed the inflnence of CEPSC on the blood concentration of CBZ,VPA.The purpose of this study was to reduce the dosage of CBZ,VPA in clinical work, release adverse effect of CBZ,VPA on the patients and provide a new select for the treatment of refractory epilepsy.The experiment was composed of three parts: (一)The research on choosing the best proportion of the combinations of CBZ,VPA and CEPSC; (二)Comparing polytherapy with monotherapy in efficacy;(三)Testing and analyzing the blood concentration of CBZ,VPA.1 We respectively compared the drug effect of three combinations of CBZ,VPA and CEPSC by determination of the threshold for localized seizure(TLS) by direct cortical stimulation in rat.The results suggested that the TLS of CBZ 30mg/kg,CEPSC 500mg/kg was significantly higher than that of other combinations at 1h,2h and 4h after drug administration(P<0.01), but was not significantly different from that of CBZ 40 mg/kg (P>0.05) ; The TLS of VPA 68mg/kg,CEPSC 500mg/kg was significantly higher than that of other combinations at 1h,2h and 4h after drug administration (P<0.01) , but was not significantly different from that of VPA 90mg/kg(P>.05). It indicated that combinations of CBZ 30mg/kg, CEPSC 500mg/kg and VPA 68mg/kg,CEPSC 500mg/kg were the best proportion combinations.2 The best proportion combinations were compared with two drugs alone on drug effect by way of using three kinds of animal convulsive model. The results suggested that the drug effect of the combinations was significantly better than that of monotherapy in maximal electroshock seizure (MES),metrazol seizure(MET) and picrotoxin seizure(PTX) in mice (P<0.01). It indicated that the combinations of CBZ,VPA and CEPSC were strong antiepileptic matter with wide spectrum of anticonvulsant activity.3 We determined the blood concentration of men after the drugs administration of CBZ, VPA and CEPSC by high performance liquid chromatography(HPLC) and analyzed the influence of CEPSC on the blood concentration of CBZ, VPA. The results suggested that the blood concentration of CBZ and VPA in combinations was not significantly different from that in monotherapy(P>0.05). It indicated that CEPSC had not any influence on the blood concentration of CBZand VPA.