Independent Unit of Experimental Neuropathophysiology, Medical University of Lublin, Jaczewskiego, 8B, Poland.
Independent Unit of Experimental Neuropathophysiology, Medical University of Lublin, Jaczewskiego, 8B, Poland.
Pharmacol Biochem Behav. 2021 Feb;201:173110. doi: 10.1016/j.pbb.2021.173110. Epub 2021 Jan 12.
Due to enhancing serotonergic and noradrenergic neurotransmission, moclobemide may influence seizure phenomena. In this study, we examined the effect of both acute and chronic treatment with moclobemide on seizures and the action of first-generation antiepileptic drugs: valproate, carbamazepine, phenobarbital and phenytoin.
The effect of moclobemide on seizures was assessed in the electroconvulsive threshold test, while its influence on antiepileptic drugs was estimated in the maximal electroshock test in mice. Undesired effects were evaluated in the chimney test (motor impairment) and step-through passive-avoidance task (long-term memory deficits). Finally, brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay.
Given acutely, moclobemide at 62.5 and 75 mg/kg increased the electroconvulsive threshold. In contrast, chronic treatment with moclobemide up to 75 mg/kg did not influence this parameter. Acute moclobemide applied at subthreshold doses (up to 50 mg/kg) enhanced the antielectroshock effects of carbamazepine, valproate and phenobarbital. Chronic moclobemide (37.5-75 mg/kg) increased the action of all four antiepileptic drugs. All revealed interactions, except these between moclobemide and phenobarbital, seem to have pharmacokinetic nature, because the antidepressant drug, either in acute or in chronic treatment, increased the brain concentrations of respective antiepileptic drugs. In terms of undesired neurotoxic effects, acute and chronic moclobemide, antiepileptic drugs, and their combinations did not produce significant motor or long-term memory impairment.
Acute and chronic therapy with moclobemide can increase the effectiveness of some antiepileptic drugs against the maximal electroshock test. In mice, this effect was, at least partially, due to pharmacokinetic interactions. So far as the results of experimental studies can be transferred to clinical conditions, moclobemide seems safe for the application in patients with epilepsy and depression. Possibly, in the case of certain antiepileptic drugs combined with moclobemide, their doses should be adjusted downwards.
由于增强了血清素能和去甲肾上腺素能神经传递，吗氯贝胺可能会影响癫痫发作现象。在这项研究中，我们研究了吗氯贝胺的急性和慢性治疗对癫痫发作的影响，以及第一代抗癫痫药物：丙戊酸钠、卡马西平、苯巴比妥和苯妥英钠的作用。
在电惊厥阈试验中评估吗氯贝胺对癫痫发作的影响，而在最大电休克试验中评估其对抗癫痫药物的影响。在烟囱试验（运动障碍）和穿梭被动回避任务（长期记忆缺陷）中评估不良反应。最后，通过荧光偏振免疫测定法确定抗癫痫药物的脑浓度。
急性给予吗氯贝胺 62.5 和 75mg/kg 可增加电惊厥阈。相反，高达 75mg/kg 的慢性吗氯贝胺治疗并不影响该参数。急性给予低于阈剂量（高达 50mg/kg）的吗氯贝胺可增强卡马西平、丙戊酸钠和苯巴比妥的抗电休克作用。慢性吗氯贝胺（37.5-75mg/kg）增加了所有四种抗癫痫药物的作用。除了吗氯贝胺和苯巴比妥之间的相互作用外，所有这些相互作用似乎都具有药代动力学性质，因为这种抗抑郁药，无论是在急性还是慢性治疗中，都增加了相应抗癫痫药物的脑浓度。就不良神经毒性作用而言，急性和慢性吗氯贝胺、抗癫痫药物及其组合并未导致明显的运动或长期记忆障碍。
急性和慢性吗氯贝胺治疗可提高一些抗癫痫药物对最大电休克试验的疗效。在小鼠中，这种作用至少部分是由于药代动力学相互作用所致。就实验研究的结果可以转移到临床条件而言，吗氯贝胺似乎对癫痫和抑郁症患者的应用是安全的。可能的情况下，在某些抗癫痫药物与吗氯贝胺联合使用时，应向下调整其剂量。
