普瑞巴林胡椒丙烯酸衍生物对戊四唑致小鼠惊厥的保护  

Protection of piperonylacrylic acid derivative of Pregabalin on pentylenetetrazole-induced convulsions in mice

作　　者：王燕 王晨慧 李胜男 李霖枫 庄晓晓 陈重华[1] 陈勇 WANG Yan;WANG Chenhui;LI Shengnan;LI Linfeng;ZHUANG Xiaoxiao;CHEN Zhonghua;CHEN Yong(West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China;School of Pharmacy,Nantong University,Nantong,Jiangsu,226001 P.R.China;Suzhou Salupurus Pharmaceutical Technology Co.,Ltd.,Suzhou,Jiangsu,215421 P.R.China)

机构地区：[1]四川大学华西药学院,四川成都610041 [2]南通大学药学院,江苏南通226001 [3]苏州康纯医药科技有限公司,江苏苏州215421

出　　处：《华西药学杂志》2022年第1期19-22,共4页West China Journal of Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(批准号:81603044);太仓市重点研发计划社会发展项目(No.TC2017SF02)。

摘　　要：目的设计并合成普瑞巴林(PGB)和胡椒丙烯酸(PPA)的缩合产物PP,以期获得抗癫痫新化合物。方法以PGB和PPA为原料,缩合得到目标化合物PP。初步评价PP在小鼠血浆、肝匀浆和脑匀浆中的稳定性。将小鼠分为模型组(生理盐水)、PGB组、PPA组、PP组和PPA+PGB组(混合药物)。给药后,以戊四唑诱导小鼠惊厥,记录各组小鼠的惊厥发作等级和全身阵挛发作潜伏期。结果制备了新化合物PP,结构经^(1)HNMR确证。PP在新鲜血浆溶液、肝匀浆和脑匀浆中2 h内的降解不显著。PP能降低戊四唑致惊厥小鼠的惊厥等级,延长全身阵挛发作的潜伏期,且与PGB组比较,两指标均无统计学差异。结论新化合物PP的抗戊四唑致惊厥作用与阳性药PGB相当,结合PP的稳定性结果考虑,其抗惊厥作用不依赖于PGB。OBJECTIVE To synthesize the condensation product of Pregabalin(PGB)and piperonylacrylic acid(PPA),and to obtain a new antiepileptic compound PP.METHODS PP was synthesized via condensation of PPA with PGB.The stability of PP in plasma solution,liver homogenates and brain homogenates of mice were preliminarily evaluated.Mice were divided into 5 groups:model group(saline),PGB group,PPA group,PP group,and PPA+PGB group(mixed drugs).After the drug administration,mice were induced convulsions by pentylenetetrazol,and convulsion scores(CS)and latencies of generalized clonic seizure of each group were recorded.RESULTS The new compound PP was synthesized,and the structure was confirmed by;HNMR.PP in fresh plasma solution,liver homogenates and brain homogenates didn’t degrade markedly within 2 h.PP significantly reduced CS and prolonged latencies of convulsive mice induced by pentylenetetrazol,and there was no significant difference between the PP group and the PGB group in CS and latencies.CONCLUSION The new compound PP has an comparable effect against convulsions induced by pentylenetetrazol in mice to the positive drug PGB.In consideration to the stability results,the anti-convulsion effect of PP doesn’t rely on PGB.

关 键 词：普瑞巴林 胡椒丙烯酸 合成 桂皮酰胺 衍生物 稳定性 戊四唑 抗惊厥 

分 类 号：R96[医药卫生—药理学]