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两种新型4-[1-(4-氟苄基)-5-咪唑基]二氢吡啶衍生物对小鼠抗惊厥作用的评价。

Evaluation of anticonvulsant effect of two novels 4-[1-(4-fluorobenzyl)- 5-imidazolyl] dihydropyridine derivatives in mice.

作者信息

Hadizadeh F, Rahimi B, Taghiabadi E, Razavi M, Karimi G

机构信息

Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, I.R. Iran.

出版信息

Res Pharm Sci. 2013 Apr;8(2):91-5.

Abstract

In this study the anticonvulsant effect of two dihydropyridine derivatives [diethyl -1,4- dihydro -2,6-dimethyl -4-(4- fluoro benzyl-2- methylthio -5- imidazolyl)-3,5- pyridine dicarboxilat (A) and diethyl -1,4-dihydro -2,6- diethyl -4-(4- fluoro benzyl-2- methylthio -5- imidazolyl)-3,5- pyridine dicarboxilat (B)] by pentylenetetrazole (PTZ) and electroshock in mice was evaluated. The latency and HLTE (hind limb tonic extensions), the duration of HLTE and the mortality protection in pentylenetetrazole test and the HLTE duration in electroshock test were assessed. Both compounds had significant differences with negative control in all doses used. There was no significant difference between nifedipine and B (96.7 and 169.2 mg/kg doses) in the starting point of HLTE and between nifedipine andA(62.2 and 108.9 mg/kg doses) in the duration of HLTE in the PTZ test. Also, there was no significant difference between nifedipine and B (96.7 and 169.2 mg/kg doses) andA(62.2 and 108.9 mg/kg doses) in electroshock test. All doses ofAand B and nifedipine showed less effect than phenytoin and valproate. This study showed that bothAand B have anticonvulsant activity in the PTZ-induced seizure model and the MES test. These compounds, thus, might be useful in the petit mal and grand mal epilepsy.

摘要

在本研究中,评估了两种二氢吡啶衍生物[二乙基-1,4-二氢-2,6-二甲基-4-(4-氟苄基-2-甲硫基-5-咪唑基)-3,5-吡啶二羧酸酯(A)和二乙基-1,4-二氢-2,6-二乙基-4-(4-氟苄基-2-甲硫基-5-咪唑基)-3,5-吡啶二羧酸酯(B)]对小鼠戊四氮(PTZ)诱发惊厥和电休克的抗惊厥作用。评估了潜伏期和后肢强直性伸展(HLTE)、HLTE持续时间以及戊四氮试验中的死亡保护率和电休克试验中的HLTE持续时间。在所有使用的剂量下,两种化合物与阴性对照均有显著差异。在PTZ试验中,硝苯地平与B(96.7和169.2mg/kg剂量)在HLTE起始点以及硝苯地平与A(62.2和108.9mg/kg剂量)在HLTE持续时间方面无显著差异。此外,在电休克试验中,硝苯地平与B(96.7和169.2mg/kg剂量)以及A(62.2和108.9mg/kg剂量)之间也无显著差异。A、B和硝苯地平的所有剂量均显示出比苯妥英和丙戊酸的效果更差。本研究表明,A和B在PTZ诱导的癫痫模型和最大电休克试验(MES)中均具有抗惊厥活性。因此,这些化合物可能对失神性癫痫和大发作癫痫有用。

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