Pietrzak Bogusława, Zwierzyńska Ewa, Krupa Agata
Department of Pharmacodynamics, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, Poland
Department of Pharmacodynamics, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, Poland.
Alcohol Alcohol. 2014 Sep-Oct;49(5):505-14. doi: 10.1093/alcalc/agu024. Epub 2014 Jun 16.
Recent research suggests a potential role for a new generation of anticonvulsant drugs, including zonisamide, in the treatment of alcohol dependence. Some elements of the central mechanism of action that zonisamide has in common with ethanol, give rise to the question of whether there is an interaction between these two agents and whether there is any risk associated with the enhanced depressive effect of these agents on the central nervous system.
This study uses a pharmaco-EEG method to examine the interaction of ethanol with zonisamide. The influence of zonisamide on the effect of ethanol on EEG of rabbits (midbrain reticular formation, hippocampus, frontal cortex) was determined. Zonisamide was administered p.o. as a single dose (20 or 60 mg/kg) or repeatedly at a dose of 30 mg/kg/day for 14 days. Ethanol was injected i.v. at a dose of 0.8 g/kg 180 min after the administration of zonisamide.
Ethanol caused an increase in the low frequencies (0.5-4 Hz) in the recording, as well as a marked decrease in the higher frequencies (13-30 and 30-45 Hz). Changes in the EEG recordings after zonisamide alone were more significant compared with these after repeated doses. In the hippocampus after single dose of drug the proportion of the low frequency (0.5-4 Hz) increased, whereas the proportion of high frequencies decreased. Combined administration of ethanol and zonisamide (60 mg/kg) resulted in a markedly synergistic effect in the examined structures. A beneficial effect of repeatedly administered zonisamide on ethanol-induced EEG changes was observed, especially in the hippocampus.
Zonisamide in repeated doses decreases the sensitivity of the hippocampus to ethanol, an observation that may be important in the treatment of alcohol addiction.
近期研究表明，包括唑尼沙胺在内的新一代抗惊厥药物在酒精依赖治疗中可能发挥作用。唑尼沙胺与乙醇在中枢作用机制上的一些共同元素，引发了这两种药物之间是否存在相互作用以及它们增强对中枢神经系统抑制作用是否存在风险的问题。
本研究采用药物脑电图方法来检测乙醇与唑尼沙胺的相互作用。测定了唑尼沙胺对乙醇对兔脑电图（中脑网状结构、海马、额叶皮质）影响的作用。唑尼沙胺口服给药，单次剂量为20或60mg/kg，或按30mg/kg/天的剂量重复给药14天。在给予唑尼沙胺180分钟后，静脉注射0.8g/kg的乙醇。
乙醇导致记录中的低频（0.5 - 4Hz）增加，以及高频（13 - 30Hz和30 - 45Hz）显著降低。与重复给药后的脑电图记录变化相比，单独使用唑尼沙胺后的变化更显著。单次给药后，海马中低频（0.5 - 4Hz）的比例增加，而高频比例降低。乙醇与唑尼沙胺（60mg/kg）联合给药在检测的结构中产生了明显的协同作用。观察到重复给药的唑尼沙胺对乙醇诱导的脑电图变化有有益作用，尤其是在海马中。
重复给药的唑尼沙胺可降低海马对乙醇的敏感性，这一观察结果在酒精成瘾治疗中可能具有重要意义。
