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新型具有心脏活性的线性甲氧基苯并三氮杂烷衍生物的抗焦虑和镇痛作用的实验评估。

Experimental Evaluation of Anxiolytic and Analgesic Properties of a New Linear Methoxyphenyltriazaalkane Derivative with Cardiotropic Activity.

机构信息

V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia.

出版信息

Bull Exp Biol Med. 2021 Apr;170(6):763-768. doi: 10.1007/s10517-021-05149-9. Epub 2021 Apr 24.

Abstract

The anxiolytic and analgesic properties of compound ALM-802, a cardiotropic linear methoxyphenyltriazaalkane derivative, combining pharmacophore elements of p-FOX inhibitors trimetazidine and ranolazine were studied in vivo. In the elevated plus-maze test, ALM-802 after acute intraperitoneal administration in doses of 1-8 mg/kg dose-dependently prevented the development of anxiety in BALB/c mice. Chronic intraperitoneal administration of ALM-802 in a dose of 2 mg/kg to alcohol-preferring rats attenuated anxiogenesis induced by ethanol withdrawal. ALM-802 demonstrated antinociceptive activity in C57BL/6 mice during thermal stimulation of nociceptors in the hot plate test and during modeling of visceral pain in the acetic acid writhing test. Thus, ALM-802 exhibits anxiolytic and analgesic properties in the dose range corresponding to its anti-ischemic and antiarrhythmic effects.

摘要

化合物 ALM-802 具有抗焦虑和镇痛作用,它是一种具有心脏作用的线性甲氧基苯并三氮烷衍生物,结合了 FOX 抑制剂曲美他嗪和雷诺嗪的药效团元素。在高架十字迷宫试验中,ALM-802 经腹腔内给药,剂量为 1-8mg/kg,呈剂量依赖性地预防 BALB/c 小鼠出现焦虑。以 2mg/kg 的剂量腹腔内给予 ALM-802 可减轻慢性给药对酒精偏好大鼠的乙醇戒断引起的焦虑症。ALM-802 在 C57BL/6 小鼠的热板试验中对伤害感受器进行热刺激和醋酸扭体试验中模拟内脏疼痛时表现出镇痛活性。因此,ALM-802 在与其抗缺血和抗心律失常作用相对应的剂量范围内具有抗焦虑和镇痛作用。

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