Naplekova P L, Narkevich V B, Voronina T A, Kudryashov N V, Kostochka L M, Kudrin V S
Eksp Klin Farmakol. 2016;79(11):3-6.
Neuropharmacological properties of LK-998 (3,4,5-trimethoxy-N'-(2,2,6,6-tetramethylpiperidin-4-yliden)benzohydrazide), a 2,2,6,6-tetramethylpiperidone de- rivative have been studied. LK-998 exhibited anxiolytic activity in doses of 10 and 20 mg/kg, significantly increasing the duration of animal staying of in open arms of the elevated plus maze as well as the number of arm entries. The efficiency of drug tested in a dose of 10 mg/kg was comparable with that of afobazole in a dose of 5 mg/kg. In marble burying test, it was also found that animals treated with LK-998 at 10 mg/kg buried a close number of balls to that as rodents treated with afobazole at 5 mg/kg. At the same time, LK-998 in doses 10 and 20 mg/kg did not produce any antidepressant action in the learned helplessness test. Thus, LK-998 in a dose of 10 mg/kg has anxiolytic and anticompulsive effects comparable to those of afobazole at a dose of 5 mg/kg. The study of potenti- al side effects of LK- 998 in a dose of 200 mg/kg (i.e., 20 times the therapeutic dose of 10 mg/kg) showed that the drug tested caused neither side effects nor symptoms of neurological deficiency within 24 hours and on longer terms (4, 10 and 14 days after administration).
已对2,2,6,6 - 四甲基哌啶酮衍生物LK - 998(3,4,5 - 三甲氧基 - N' - (2,2,6,6 - 四甲基哌啶 - 4 - 亚基)苯甲酰肼)的神经药理学特性进行了研究。LK - 998在10毫克/千克和20毫克/千克的剂量下表现出抗焦虑活性,显著增加了动物在高架十字迷宫开放臂停留的时间以及进入臂的次数。10毫克/千克剂量的受试药物的效果与5毫克/千克剂量的阿伏唑相当。在大理石埋藏试验中还发现,用10毫克/千克的LK - 998处理的动物埋藏的球数与用5毫克/千克的阿伏唑处理的啮齿动物相近。同时,10毫克/千克和20毫克/千克剂量的LK - 998在习得性无助试验中未产生任何抗抑郁作用。因此,10毫克/千克剂量的LK - 998具有与5毫克/千克剂量的阿伏唑相当的抗焦虑和抗强迫作用。对200毫克/千克剂量(即10毫克/千克治疗剂量的20倍)的LK - 998潜在副作用的研究表明,受试药物在24小时内以及更长时间(给药后4、10和14天)既未引起副作用也未出现神经功能缺损症状。