Val'dman E A, Nerobkova L N, Voronina T A
Laboratory of Psychopharmacology, Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiiskaya ul. 8, Moscow, 125315 Russia.
Eksp Klin Farmakol. 2004 Jan-Feb;67(1):7-10.
N-(Adamant-2-yl)hexamethyleneimine hydrochloride (hemantane) is a new potential antiparkinsonian drug with a complex mechanism of action. The drug exhibits the properties of a low-affinity blocker of the ion channels of NMDA receptors, increases the dopamine content in striatum, and inhibits monoamine oxidases (MAO-B). This combination of properties suggests that hemantane can also possess neuroprotector properties. In this context, the ability of hemantane to prevent from the development of MPTP neurotoxin action on the locomotor activity in mice and the EEG activity in rats has been studied. Preliminary single (and the more so, repeated over a period of 5 days) peroral administration of hemantane in a dose of 10 mg/kg significantly reduced the manifestations of MPTP-induced oligokinesia in C57BL/6 mice. Acute of subchronic (7-day) pretreatment with hemantane prevented the development of EEG changes typical of parkinsonism. The results of statistical EEG data processing showed that a systemic introduction of MPTP (30 mg/kg) on the background of hemantane pretreatment produced no reliable changes against control characteristics. Thus, hemantane is capable of protecting experimental animals from MPTP neurotoxicity.
盐酸N-(金刚烷-2-基)六亚甲基亚胺(海金刚烷)是一种作用机制复杂的新型潜在抗帕金森病药物。该药物具有NMDA受体离子通道低亲和力阻断剂的特性,能增加纹状体中的多巴胺含量,并抑制单胺氧化酶(MAO-B)。这些特性的组合表明海金刚烷也可能具有神经保护特性。在此背景下,研究了海金刚烷预防MPTP神经毒素对小鼠运动活性和大鼠脑电图活性影响的能力。以10 mg/kg的剂量单次(更不用说连续5天重复给药)口服海金刚烷,可显著减轻C57BL/6小鼠中MPTP诱导的运动迟缓表现。海金刚烷急性或亚慢性(7天)预处理可预防帕金森病典型脑电图变化的发生。脑电图数据的统计处理结果表明,在海金刚烷预处理的背景下全身注射MPTP(30 mg/kg),与对照特征相比未产生可靠变化。因此,海金刚烷能够保护实验动物免受MPTP神经毒性的影响。