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两种 1,5-苯二氮䓬类化合物在小鼠体内的神经药理学筛选。

Neuropharmacological screening of two 1,5-benzodiazepine compounds in mice.

机构信息

Laboratoire de pharmacologie, faculté de médecine de Monastir, 5019 Monastir, Tunisia.

出版信息

C R Biol. 2010 Mar;333(3):214-9. doi: 10.1016/j.crvi.2009.09.015. Epub 2010 Mar 4.

Abstract

This work investigates whether the two 1,5-benzodiazepine compounds: 4-(2-hydroxyphenyl)-1,5-benzodiazepin-2-one (RG0501) and Benzopyrano [4,3-c] 1,5-benzodiazepine (RG0502) have any neuropharmacological activities. Diazepam and Flunitrazepam were used as drug references. The investigational 1,5-BDZ were tested in vivo for potentiating hexobarbital-induced sleep and pentylenetetrazole (PTZ)-induced seizures. Our study demonstrated that the increase of sleep duration was significantly higher with RG0501 as compared to RG0502. However, RG0502 anticonvulsant effect was more pronounced than that of RG0501 in the range dose of 6.25-37.5 mg.kg(-1). From the 50 mg.kg(-1) dose, RG0502 offered a protection against clonic-tonic seizures as well as lethality (p< or =0.05). The results showed that the required doses to obtain a pharmacological activity were more than those of the references. This difference could be related to the lack of specific substituants responsible for the pharmacological activity in the tested compounds.

摘要

这项工作研究了两种 1,5-苯并二氮杂卓化合物:4-(2-羟基苯基)-1,5-苯并二氮杂卓-2-酮 (RG0501) 和苯并吡喃[4,3-c] 1,5-苯并二氮杂卓 (RG0502) 是否具有任何神经药理学活性。地西泮和氟硝西泮被用作药物参考。研究中的 1,5-BDZ 在体内被测试以增强戊巴比妥诱导的睡眠和戊四氮 (PTZ) 诱导的癫痫发作。我们的研究表明,与 RG0502 相比,RG0501 增加睡眠时间的效果更为显著。然而,在 6.25-37.5 mg.kg(-1) 的剂量范围内,RG0502 的抗惊厥作用比 RG0501 更为明显。从 50 mg.kg(-1) 的剂量开始,RG0502 对强直阵挛性癫痫发作以及致死性具有保护作用 (p<或=0.05)。结果表明,获得药理学活性所需的剂量高于参考物。这种差异可能与测试化合物中缺乏负责药理学活性的特定取代基有关。

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