Borowicz Kinga K, Swiader Mariusz, Luszczki Jarogniew, Czuczwar Stanislaw J
Department of Pathophysiology and Department of Pharmacology and Toxicology, Medical University, and Isotope Laboratory, Institute of Agricultural Medicine, Lublin, Jaczewskiego, Poland.
Epilepsia. 2002 Sep;43(9):956-63. doi: 10.1046/j.1528-1157.2002.34301.x.
The objective of this study was the isobolographic evaluation of the interactions between the novel antiepileptic drug (AED) gabapentin (GBP) and a number of other AEDs against electroconvulsion-induced convulsions in mice.
Electroconvulsions were produced by means of an alternating current (ear-clip electrodes, 0.2-s stimulus duration, tonic hindlimb extension taken as the end point). Adverse effects were evaluated with the chimney test (motor performance) and passive-avoidance task (long-term memory). Plasma levels of AEDs were measured by immunofluorescence or high-pressure liquid chromatography.
GBP (< or =50 mg/kg) remained ineffective on the electroconvulsive threshold. According to the isobolographic analysis, GBP appears to act synergistically with carbamazepine, valproate, phenytoin, phenobarbital (PB), lamotrigine (LTG), and LY 300164. The pharmacokinetic events may be responsible for the interactions of GBP/PB and GBP/LTG, because only PB and LTG significantly elevated the plasma concentration of this AED. Conversely, GBP did not affect the plasma levels of other AEDs used in this study. No adverse effects were induced by combinations of GBP with these AEDs.
The isobolographic analysis revealed that combinations of GBP with other AEDs generally results in synergistic (supraadditive) interactions.
本研究的目的是采用等效线图分析法评估新型抗癫痫药物（AED）加巴喷丁（GBP）与其他多种AED联合应用对小鼠电惊厥诱发的抽搐的相互作用。
通过交流电（耳夹电极，刺激持续时间0.2秒，以强直性后肢伸展为终点）诱发电惊厥。采用烟囱试验（运动性能）和被动回避任务（长期记忆）评估不良反应。通过免疫荧光或高压液相色谱法测定AED的血浆浓度。
GBP（≤50mg/kg）对电惊厥阈值无影响。根据等效线图分析，GBP似乎与卡马西平、丙戊酸盐、苯妥英、苯巴比妥（PB）、拉莫三嗪（LTG）和LY 300164具有协同作用。药代动力学事件可能是GBP/PB和GBP/LTG相互作用的原因，因为只有PB和LTG显著提高了这种AED的血浆浓度。相反，GBP不影响本研究中使用的其他AED的血浆水平。GBP与这些AED联合应用未诱发不良反应。
等效线图分析显示，GBP与其他AED联合应用通常会产生协同（超相加）相互作用。
