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[一种新型腺嘌呤衍生物的某些药理特性研究]

[Study of some pharmacological properties of a new adenine derivative].

作者信息

Ozerov A A, Motin V G, Iasnetsov Vik V, Karsanova S K, Ivanov Iu V, Chel'naia N A

出版信息

Eksp Klin Farmakol. 2014;77(10):15-8.

Abstract

It is established that the new compound, 9-[2-(4-isopropylphenoxy)ethyl]adenine (9-IPE-adenine) in a dose of 10 mg/kg per day produces neuroprotective effect in rats with brain ischemia model. 9-IPE-adenine decreased the neurologic deficiency 1.2 times more effectively (p < 0.05) than the reference drug mexidol in analogous dose, and had equal effect with this drug at 25 mg/kg per day on the neurologic deficiency and survival of animals. Electrophysiological studies in hippocampal slices in rats showed that 9-IPE-adenine depressed orthodromic population spikes in CA1 area by 42 ± 4%. Non-competitive antagonist of NMDA receptor complex MK-801, in contrast to D-AP5 (competitive NMDA receptor antagonist) and CNQX (competitive AMPA receptor antagonist), enhanced the depressive effect of the new drug more than two times. These ese results are indicative of the ability of 9-IPE-adenine to modulate the ion channel of NMDA receptor complex.

摘要

已证实,新型化合物9-[2-(4-异丙基苯氧基)乙基]腺嘌呤(9-IPE-腺嘌呤)以每日10毫克/千克的剂量对脑缺血模型大鼠产生神经保护作用。9-IPE-腺嘌呤降低神经功能缺损的效果比同等剂量的参比药物美西多有效1.2倍(p<0.05),并且在每日25毫克/千克时,其对动物神经功能缺损和存活率的影响与该药物相当。对大鼠海马切片进行的电生理研究表明,9-IPE-腺嘌呤使CA1区的顺向群体峰电位降低了42±4%。与D-AP5(竞争性NMDA受体拮抗剂)和CNQX(竞争性AMPA受体拮抗剂)不同,NMDA受体复合物的非竞争性拮抗剂MK-801使这种新药的抑制作用增强了两倍多。这些结果表明9-IPE-腺嘌呤具有调节NMDA受体复合物离子通道的能力。

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