Department of Occupational Medicine, Medical University of Lublin, Lublin, Poland.
Department of Toxicology and Food Safety, Institute of Rural Health, Lublin, Poland.
Pharmacol Rep. 2024 Feb;76(1):216-222. doi: 10.1007/s43440-023-00555-4. Epub 2023 Nov 28.
Anticonvulsant effects of imperatorin (IMP) have been experimentally confirmed earlier, but no information is available on the interaction profiles of this naturally occurring coumarin when combined with novel antiseizure medication (ASMs). This study aimed to determine the effects of IMP on the anticonvulsant effects of lacosamide (LCM), oxcarbazepine (OXC), pregabalin (PGB), and topiramate (TPM) in the maximal electroshock-induced seizure (MES) model in mice.
The anticonvulsant effects exerted by novel ASMs (LCM, OXC, PGB, and TPM) when combined with constant doses of IMP (25 and 50 mg/kg) underwent isobolographic transformation to precisely classify the observed interactions in the mouse MES model. Total brain concentrations of ASMs were measured with high-pressure liquid chromatography to exclude the pharmacokinetic nature of interactions among IMP and the tested ASMs.
IMP (50 mg/kg) significantly enhanced (p < 0.01) the anticonvulsant potency of LCM, OXC, PGB, and TPM in the mouse MES model. IMP (25 mg/kg) mildly potentiated the anticonvulsant action of LCM, OXC, PGB, and TPM, but no statistical significance was reported for these combinations. The isobolographic transformation of data from the MES test revealed that the interactions of novel ASMs with IMP were additive. Moreover, IMP (50 mg/kg) did not affect the total brain content of any of the novel ASMs in experimental mice.
The additive interactions of IMP with LCM, OXC, PGB, and TPM in the mouse MES model accompanied by no pharmacokinetic changes in the total brain content of ASMs are worthy of recommendation for further studies.
先前已通过实验证实了欧前胡素（IMP）的抗惊厥作用，但尚无关于这种天然香豆素与新型抗癫痫药物（ASMs）联合使用时相互作用特征的信息。本研究旨在确定IMP 对拉考沙胺（LCM）、奥卡西平（OXC）、普瑞巴林（PGB）和托吡酯（TPM）在最大电休克诱导的癫痫发作（MES）模型中抗惊厥作用的影响。
新型 ASMs（LCM、OXC、PGB 和 TPM）与固定剂量的 IMP（25 和 50mg/kg）联合使用时所产生的抗惊厥作用经过等辐射分析转换，以准确分类在小鼠 MES 模型中观察到的相互作用。采用高压液相色谱法测定 ASMs 的总脑浓度，以排除 IMP 和所测试 ASMs 之间相互作用的药代动力学性质。
IMP（50mg/kg）显著增强了（p<0.01）LCM、OXC、PGB 和 TPM 在小鼠 MES 模型中的抗惊厥作用。IMP（25mg/kg）轻度增强了 LCM、OXC、PGB 和 TPM 的抗惊厥作用，但这些组合没有统计学意义。MES 测试数据的等辐射分析转换显示，新型 ASMs 与 IMP 的相互作用是相加的。此外，IMP（50mg/kg）不影响实验小鼠中任何新型 ASMs 的总脑含量。
IMP 与 LCM、OXC、PGB 和 TPM 在小鼠 MES 模型中的相加相互作用，同时不影响 ASMs 的总脑含量的药代动力学变化，值得进一步研究。
